Osteogenesis imperfecta with repeated simultaneous bilateral proximal tibial epiphyseal injuries caused by minor trauma: A case report and literature review.

INTRODUCTION: Proximal tibial epiphyseal injuries are rare, accounting for 0.5-3 % of all epiphyseal injuries, of which bilateral cases are extremely rare. Only five cases of bilateral proximal tibial epiphyseal injuries have so far been reported in patients with osteogenesis imperfecta. We herein present a case of repeated bilateral proximal tibial epiphyseal injuries with a diagnosis of osteogenesis imperfecta. We also performed a literature review of 46 cases of bilateral proximal tibial epiphyseal injuries reported since 1955, including 5 of osteogenesis imperfecta. PRESENTATION OF CASE: A 10-year-old boy repeatedly sustained bilateral simultaneous proximal tibial epiphyseal injuries due to minor trauma. Blue sclera was noted and, thus, genetic testing was performed and revealed osteogenesis imperfecta. After the fourth injury, we performed internal fixation with cannulated cancellous screw bilaterally. The patient had a short stature and the marked loss of bone density; therefore, the screw was kept in place until epiphyseal closure and bisphosphonate and human growth hormone were administered to prevent re-fracture and increase bone density and the growth rate. DISCUSSION: The literature review revealed that the mean age of injury was 11.2 years for osteogenesis imperfecta cases and 14.9 years for non-osteogenesis imperfecta cases, with the former being injured at a younger age. CONCLUSION: Osteogenesis imperfecta often causes diaphyseal fractures, which may be attributed to the fragility of the epiphyseal line. Therefore, the possibility of osteogenesis imperfecta needs to be considered when treating patients with epiphyseal injuries at rare sites, particularly younger children.

Effects of CO2 on time-dependent changes in cardiorespiratory functions under sustained hypoxia.

Hypercapnia in addition to hypoxia affects the mammalian cardiorespiratory system and has been suggested to exert its effects on cardiorespiratory function by slightly different mechanisms to hypoxia. In the present study, we examined cardiorespiratory changes in urethane-anesthetized rats under hypocapnic (Hypo, 10% O2), isocapnic (Iso, 10% O2 and 4% CO2), and hypercapnic (Hyper, 10% O2 and 8% CO2) hypoxia for 2 h to clarify the effects of CO2 on sustained hypoxia-induced cardiorespiratory responses. Respiratory frequency increased the most in Hypo and tidal volume in Hyper. Minute ventilation, a product of respiratory frequency and tidal volume, increased the most in the latter group. Regarding cardiovascular variables during the hypoxic exposure period, heart rate and mean blood pressure both markedly decreased in Hypo. However, decreases in these parameters were small in Iso, and both increased over the pre-exposure level in Hyper. The present results suggest that CO2 interferes with the hypoxia-activated neural pathway via another pathway under sustained exposure to hypoxia.

Sports-Related Motor Processing at Different Rates of Force Development.

How does our brain manage to process vast quantities of sensory information that define movement performance? By extracting the required movement parameters for which brain dynamics are, inter alia, assumed to be functionally related to, we used electroencephalography to investigate motor-related brain oscillations. Visually guided movement (i.e., motor) tasks at explosive, medium and slow rates of force development (RFD) revealed increased broad-band activity at explosive RFD, whereas decreasing activity could be observed during both intermediate and slow RFD. Moreover, a continuously decreasing activity pattern from faster to slower RFD and a return to baseline activity after full muscle relaxation was found. We suggest oscillatory activity to desynchronize in sensorimotor demanding tasks, whereas task-specific synchronization mirrors movement acceleration. The pre/post-stimulus activity steady state may indicate an inhibitory baseline that provides attentional focus and timing.

Recognition capability of one's own skilled movement is dissociated from acquisition of motor skill memory.

When we have rehearsed a movement using an object, we can reproduce the movement without holding the object. However, the reproduced movement sometimes differs from the movement holding a real object, likely because movement recognition is inaccurate. In the present study, we tested whether the recognition capability was dissociated from the acquisition of motor skill memory. Twelve novices were asked to rotate two balls with their right hand as quickly as possible; they practiced the task for 29 days. To evaluate recognition capability, we calculated the difference in coordination pattern of all five digits between the ball-rotation movement and the reproduced movement without holding balls. The recognition capability did not change within the first day, but improved after one week of practice. On the other hand, performance of the ball rotation significantly improved within the first day. Since improvement of performance is likely associated with acquisition of motor skill memory, we suggest that recognition capability, which reflects the capability to cognitively access motor skill memory, was dissociated from the acquisition of motor skill memory. Therefore, recognition of one's own skilled movement would rely on a hierarchical structure of acquisition of motor skill memory and cognitive access to that memory.

Differences in the expression of catecholamine-synthesizing enzymes between vesicular monoamine transporter 1- and 2-immunoreactive glomus cells in the rat carotid body.

Vesicular monoamine transporters (VMAT) 1 and 2 are responsible for monoamine transportation into secretary vesicles and are tissue-specifically expressed in central and peripheral monoaminergic tissues, including the carotid body (CB). The aim of the present study was to examine the expression of catecholamine-synthesizing enzymes in VMAT1- and VMAT2-immunoreactive glomus cells in the rat CB using multiple immunolabeling. The expression of VMAT1 and VMAT2 mRNA in the CB was confirmed by RT-PCR. Immunohistochemistry revealed that VMAT1 immunoreactivity was predominant in glomus cells rather than VMAT2 immunoreactivity. Glomus cells with VMAT1 immunoreactivity exhibited weak/negative VMAT2 immunoreactivity, and vice versa. Immunoreactivities for VMAT1 and tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis, were co-localized in the same glomus cells and a positive correlation was confirmed between the two immunoreactivities (Spearman's coefficient = 0.82; p <  0.05). Although some glomus cells showed co-localization of VMAT2 and dopamine ß-hydroxylase immunoreactivity, the biosynthetic enzyme for noradrenaline, VMAT2 immunoreactivity appeared to be less associated with both catecholamine-synthesizing enzymes as indicated by a correlation analysis (TH: Spearman's coefficient = 0.38, DBH: Spearman's coefficient = 0.26). These results indicate that heterogeneity on functional role would exist among glomus cells in terms of VMAT isoform and catecholamine-synthesizing enzymes expression.

Vesicular nucleotide transporter-immunoreactive type I cells associated with P2X3-immunoreactive nerve endings in the rat carotid body.

ATP is the major excitatory transmitter from chemoreceptor type I cells to sensory nerve endings in the carotid body, and has been suggested to be released by exocytosis from these cells. We investigated the mRNA expression and immunohistochemical localization of vesicular nucleotide transporter (VNUT) in the rat carotid body. RT-PCR detected mRNA expression of VNUT in extracts of the tissue. Immunoreactivity for VNUT was localized in a part of type I cells immunoreactive for synaptophysin (SYN), but not in glial-like type II cells immunoreactive for S100 and S100B. Among SYN-immunoreactive type I cells, VNUT immunoreactivity was selectively localized in the sub-population of tyrosine hydroxylase (TH)-immunorective type I cells associated with nerve endings immunoreactive for the P2X3 purinoceptor; however, it was not detected in the sub-population of type I cells immunoreactive for dopamine beta-hydroxylase. Multi-immunolabeling for VNUT, P2X3, and Bassoon revealed that Bassoon-immunoreactive products were localized in type I cells with VNUT immunoreactivity, and accumulated on the contact side of P2X3-immunoreactive nerve endings. These results revealed the selective localization of VNUT in the subpopulation of TH-immunoreactive type I cells attached to sensory nerve endings and suggested that these cells release ATP by exocytosis for chemosensory transmission in the carotid body.

Brain Activity Underlying Muscle Relaxation.

Fine motor control of not only muscle contraction but also muscle relaxation is required for appropriate movements in both daily life and sports. Movement disorders such as Parkinson's disease and dystonia are often characterized by deficits of muscle relaxation. Neuroimaging and neurophysiological studies suggest that muscle relaxation is an active process requiring cortical activation, and not just the cessation of contraction. In this article, we review the neural mechanisms of muscle relaxation, primarily utilizing research involving transcranial magnetic stimulation (TMS). Several studies utilizing single-pulse TMS have demonstrated that, during the relaxation phase of a muscle, the excitability of the corticospinal tract controlling that particular muscle is more suppressed than in the resting condition. Other studies, utilizing paired-pulse TMS, have shown that the intracortical inhibition is activated just before muscle relaxation. Moreover, muscle relaxation of one body part suppresses cortical activities controlling other body parts in different limbs. Therefore, the cortical activity might not only be a trigger for muscle relaxation of the target muscles but could also bring about an inhibitory effect on other muscles. This spread of inhibition can hinder the appropriate contraction of muscles involved in multi-limb movements such as those used in sports and the play of musical instruments. This may also be the reason why muscle relaxation is so difficult for beginners, infants, elderly, and the cognitively impaired.

The difference in hemodynamic responses between dominant and non-dominant hands during muscle contraction and relaxation: An fNIRS study.

The present study used functional near-infrared spectroscopy (fNIRS), and investigated the differences in neural activation of ipsi- or contralateral hemispheres between right dominant and left non-dominant hands among right-handed subjects using consecutive motor tasks with muscle contraction and relaxation. The subjects performed tasks under four conditions: (1) right hand up (R-Up), (2) left hand up (L-Up), (3) right hand down (R-Down), and (4) left hand down (L-Down). The peak amplitude of oxy-Hb was significantly larger at the contralateral than ipsilateral hemisphere in the premotor area (PM) under the R-Up condition, and no significant differences were observed between contra- and ipsilateral hemispheres under the L-Up condition. In addition, the peak amplitude was more negative at the contra- than ipsilateral hemisphere in the PM under the R-Down condition, while the peak amplitude was significantly more negative at the ipsi- than contralateral hemisphere in the PM under the L-Down condition. These results suggest that the PM of the left hemisphere among right-handed subjects plays an important role in muscle contraction and relaxation with force control.

Remote effects on corticospinal excitability during motor execution and motor imagery.

We investigated the remote effect on corticospinal excitability of resting left and right hand muscles during motor execution and motor imagery when performing left or right foot plantar flexion. Fifteen right-handed subjects performed two conditions with three tasks: Condition (Motor Execution (ME) vs. Motor Imagery (MI)): Task (Control, Ipsilateral, and Contralateral). From the left and right first dorsal interosseous, motor evoked potentials (MEPs) elicited by a single-pulse transcranial magnetic stimulation (TMS) to the left or right primary motor cortices (M1) were recorded under all six trials. MEP amplitudes were significantly larger under the ME than MI condition, irrespective of hands and tasks. MEP amplitudes were also the largest during the Contralateral tasks, irrespective of the condition and hands. The correlation analysis showed that MEP amplitudes were significantly correlated between ME and MI conditions with both left and right hands. Our results indicate that the magnitude of the remote effect on corticospinal excitability of hand muscles differs between motor execution and motor imagery, and between ipsi- and contralateral limbs, when performing foot plantar flexion.

Walking and finger tapping can be done with independent rhythms.

Rhythmic movements occur in many aspects of daily life. Examples include clapping the hands and walking. The production of two independent rhythms with multiple limbs is considered to be extremely difficult. In the present study we evaluated whether two different, independent rhythms that involved finger tapping and walking could be produced. In Experiment I, twenty subjects that had no experience of musical instrument training performed rhythmic finger tapping with the right index finger and one of four different lower limb movements; (1) self-paced walking, (2) given-paced walking, (3) alternative bilateral heel tapping from a sitting position, and (4) unilateral heel tapping with the leg ipsilateral to the tapping finger from a sitting position. The target intervals of finger tapping and heel strikes for walking step/heel tapping were set at 375 ms and 600 ms, respectively. The even distribution of relative phases between instantaneous finger tapping and heel strike was taken as the criteria of independency for the two rhythms. In the self-paced walking and given-paced walking tasks, 16 out of 20 subjects successfully performed finger tapping and walking with independent rhythms without any special practice. On the other hand, in the bipedal heels striking and unipedal heel striking tasks 19 subjects failed to perform the two movements independently, falling into interrelated rhythms with the ratio mostly being 2:1. In Experiment II, a similar independency of finger tapping and walking at a given pace was observed for heel strike intervals of 400, 600, and 800 ms, as well as at the constant 375 ms for finger tapping. These results suggest that finger tapping and walking are controlled by separate neural control mechanisms, presumably with a supra-spinal locus for finger tapping, and a spinal location for walking.

Effects of longer vs. shorter timed movement sequences on alpha motor inhibition when combining contractions and relaxations.

Alpha inhibitory processes reflect motor stimuli by either increasing or decreasing amplitude (i.e., power). However, the functional role and interplay of event-related alpha oscillations remains a regulatory domain that has not been sufficiently addressed, particularly with respect to different muscle activation types and durations in consecutive movement (i.e., motor) tasks. The aim of this study was to investigate alpha-band activity (7-13 Hz) in longer vs. shorter timed isometric muscle activations at distinct torques (20% and 40% of maximum voluntary contraction, MVC) when combined in one motor task sequence. In a randomized and controlled design, 18 healthy males volunteered to perform 40 longer (i.e., 6 s) and 40 shorter (i.e., 3 s) motor task sequences, each comprising isometric contractions (i.e., palmar flexion) from baseline to 20% and 40% MVC subsequent to relaxations from 40% and 20% MVC to baseline. Continuous, synchronized EEG, EMG and torque recordings served to determine alpha-band activity over task-relevant motor areas at distinct torques. Main findings revealed increases in alpha activity during subsequent progressive muscle relaxation (from 20% MVC in long and short: p < .001; from 40% MVC in short: p < .05), whereas modulations in relevant motor areas were not significant (p = .84). It may be suggested that an active task-relevant inhibitory process indicates motor task sequence-related relaxation mirrored by an increasing alpha activity.

Establishment and Characterization of a Novel Human Clear-cell Sarcoma of Soft-tissue Cell Line, RSAR001, Derived from Pleural Effusion of a Patient with Pleural Dissemination.

BACKGROUND/AIM: Clear cell sarcoma (CCS) of soft tissue is exceedingly rare and frequently exhibits aggressive behavior. Toward the goals of improving the aggressive course and poor prognosis of CCS, and establish new therapeutic methods, molecular genetic and biological characterizations of CCS are required. MATERIALS AND METHODS: A new human CCS cell line (designated RSAR001) was established from the pleural effusion of a 44-year-old man with multiple lung metastases and pleural dissemination. The cell line and its xenograft were characterized including their morphology, immunohistochemistry, cytogenetic analysis, reverse transcription-polymerase chain reaction, direct sequencing analysis, and fluorescence in situ hybridization analysis. RESULTS: The cell line has been maintained for over 12 months with more than 50 passages. RSAR001 cells exhibited a fascicular or diffuse growth pattern of short spindle- or oval-shaped cells with clear cytoplasm in heterotransplanted tumor, that was similar to the primary tumor. Immunophenotypically, RSAR001 cells in vitro and in vivo exhibited almost the same characteristics as the primary tumor. Cytogenetic analyses revealed a translocation, t(12;22)(q13;q12). Reverse transcription-polymerase chain reaction and direct sequencing analysis detected transcripts of the Ewing sarcoma breakpoint region 1-activating transcription factor 1 (EWSR1-ATF1) type 1 fusion gene. Fluorescence in situ hybridization using a break-apart probe for the EWSR1 gene on 22q12 showed a rearrangement. CONCLUSION: These findings indicate that the RSAR001 cell line harbors EWSR1-ATF1 type 1 chimeric fusion gene, which is specific to CCS. RSAR001 cells might be useful for investigating biological behaviors and developing new treatments such as molecular-targeting antitumor drugs or immunological drugs for CCS.

Time-dependent changes in cardiorespiratory functions of anesthetized rats exposed to sustained hypoxia.

Although cardiovascular responses may be altered by respiratory changes under prolonged hypoxia, the relationship between respiratory and cardiovascular changes remains unknown. The aim of the present study is to clarify cardiorespiratory changes in anesthetized rats during and after hypoxic conditions using simultaneous recordings of cardiorespiratory variables with 20-sec recording intervals. After air breathing for 20 min (pre-exposure period), rats were subjected to 10% O2 for 2 h (hypoxic exposure period) and then air for 30 min (recovery period). Minute ventilation (VE), respiratory frequency, tidal volume, arterial blood pressure (BP), and heart rate (HR) were continuously monitored during the experimental period. Just after hypoxic exposure, VE, BP, and HR exhibited an overshoot, undershoot, and overshoot followed by a decrease, respectively. During the remaining hypoxic exposure period, continuous high VE and low BP were observed, whereas HR re-increased. In the recovery period, VE, BP, and HR showed an undershoot, increase, and decrease followed by an increase, respectively. These results suggest that the continuation of enhanced VE and re-increased HR, probably, due to carotid body excitation and accompanying sympathetic activation, during the late period of hypoxic exposure are protective responses to avoid worsening hypoxemia and further circulatory insufficiencies under sustained hypoxia.

Enhanced biopharmaceutical effects of tranilast on experimental colitis model with use of self-micellizing solid dispersion technology.

The present study aimed to clarify the applicability of a self-micellizing solid dispersion of tranilast (SMSD/TL) to the treatment of inflammatory bowel diseases (IBD) using an experimental colitis model. SMSD/TL with several loading amounts ranging from 10 to 50% was prepared using a wet-milling system. The physicochemical properties of SMSD/TL were evaluated in terms of the dissolution behavior, morphology, and particle size distribution. Animal studies were conducted to evaluate oral bioavailability in rats and anti-inflammatory effects in a rat model of chemically induced colitis. SMSD/TL with drug loading of 15% (SMSD/TL15) showed enhanced dissolution behavior at pH 1.2, compared with other tested other formulations. After the dispersion of SMSD/TL15 in deionized water, fine micelles formed with an average diameter of 137 nm. SMSD/TL15 (10 mg-TL/kg) exhibited about 147- and 34-fold greater value for Cmax and the area under the curve of plasma concentration vs. time than crystalline TL, respectively. Although the anti-inflammatory effect on the colitis model was very limited in the crystalline TL (2 mg/kg) group, inflammatory events, such as myeloperoxidase activity and thickening of the submucosa in colon tissues, were significantly suppressed in the SMSD/TL15 (2 mg-TL/kg) group. Based on these findings, SMSD/TL might be a more efficacious dosage option for improved IBD treatment.

Performance control in one consecutive motor task sequence - Αpproaching central neuronal motor behaviour preceding isometric contraction onsets and relaxation offsets at lower distinct torques.

OBJECTIVE: Motor-related cortical potentials (MRCP) often compared separated muscle activations; however, MRCP preceding combined contraction onsets and relaxation offsets of one consecutive motor task sequence remain to be elucidated. METHODS: Twelve healthy males (27.92±4.33 years, 181.83±7.15 cm, 84.58±7.15 kg) performed 40 submaximal isometric right-limb wrist flexions (i.e. motor task sequences). Each motor task sequence combined timed contractions to and relaxations from distinct torque levels, i.e. 20% and 40% of maximum voluntary contractions (MVC). Synchronized continuous EEG (32 Ag/AgCl-electrodes mounted over motor-related areas) and EMG (i.e. flexor carpi radialis, FCR) recordings served to detect torque level-on/offsets for MRCP analyses. RESULTS: Motor task sequences were accurately maintained with participants' mean values of FCR muscle activity revealing no signs of fatigue (p⟩0.05). Main findings (i.e. readiness potential) were larger amplitudes over frontal electrode sites (p⟨0.05) preceding contractions compared to relaxations, whereas amplitudes were larger (i.e. peak) over centro-parietal electrode sites (p⟨0.05) preceding 40% compared to 20% MVC. CONCLUSION: When performed in one consecutive motor task sequence, controlling the production as well as the releasing of force may require similar proprioceptive and visuo-motor processing preceding the same force level (i.e. 20% or 40%); however, this is irrespective of the muscle activation type (i.e. contraction or relaxation).

Effect of salient points in movements on the constraints in bimanual coordination.

The relative-salience hypothesis has been proposed as a possible explanation for the stability of bimanual coordination. This explanation proceeds from a psychological viewpoint and is based on the following tenets: (1) cyclic joint motions involving two movements are conceived of as a unified event, (2) if a "single" point in each movement is seen as the most salient, the salient points of the two movements prefer to go together, and (3) in other cases, a unified event will be constrained by movement direction. In this investigation, we examined whether the relative-salience hypothesis could predict the type of constraint (i.e., action coupling vs movement direction) for various bimanual coordination movements. Participants performed six different joint movements in synchrony with metronome beats. Both index finger flexion/extension and forearm pronation/supination had a "single" salient point (JMsingleSP), the others had "two" salient points (JMtwoSP). Then, we applied the relative-salience hypothesis to four bimanual coordinations. The coupling of simultaneous forearm pronation was more stable than alternate pronation. Similarly, the coupling of finger flexion and forearm pronation was more stable than that of finger flexion and forearm supination. For the coordination of radial flexion/ulnar flexion and index finger flexion/extension as well as forearm pronation/supination and radial flexion/ulnar flexion, symmetric movements were more stable than asymmetric movements. The results indicated that the stability of bimanual coordination was predominantly constrained by coupling of salient points when using two JMsingleSP and it was predominantly constrained by movement direction when coordinating JMsingleSP and JMtwoSP. Thus, the relative-salience hypothesis was supported.

Motor imagery of voluntary muscle relaxation of the foot induces a temporal reduction of corticospinal excitability in the hand.

The object of this study was to clarify how the motor imagery of foot muscle relaxation influences corticospinal excitability for the ipsilateral hand. Twelve participants volitionally relaxed their right foot from a dorsiflexed position (actual relaxation), or imaged the same movement (imagery relaxation) in response to an auditory cue. Transcranial magnetic stimulation (TMS) was delivered to the hand area of the left primary motor cortex at different time intervals after an auditory cue. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased during both actual relaxation and imagery relaxation as compared with those of the resting control. A correlation of MEP amplitude between actual relaxation and imagery relaxation was observed. Our findings indicate that motor imagery of muscle relaxation of the foot induced a reduction of corticospinal excitability in the ipsilateral hand muscles. This effect is likely produced via the same mechanism that functions during actual muscle relaxation.

Corticospinal excitability for hand muscles during motor imagery of foot changes with imagined force level.

The object of this study was to clarify whether corticospinal excitability controlling hand muscles changes concurrently with increases in the imagined contraction level of foot dorsiflexion. Twelve participants performed actual and imagined dorsiflexion of their right foot at three different EMG levels (10, 40 or 80% of the maximum voluntary contraction). During isometric actual- or imagined- dorsiflexion, transcranial magnetic stimulation (TMS) was delivered to the right hand area of the left primary motor cortex. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). During actual contraction, MEP amplitudes of ECR and FCR increased with an increased EMG level of dorsiflexion. Similarly, during imagery contraction, MEP amplitudes of ECR and FCR increased with the intensity of imagery contraction. Furthermore, a correlation between MEP amplitude during actual contraction and imagery contraction was observed for both ECR and FCR. Motor imagery of foot contraction induced an enhancement of corticospinal excitability for hand muscles that was dependent on the imagined contraction levels, just as what was observed when there was an actual contraction.

Age-related changes in immunoreactivity for dopamine ß-hydroxylase in carotid body glomus cells in spontaneously hypertensive rats.

The purpose of this study was to investigate immunoreactivity for dopamine ß-hydroxylase (DBH) and tyrosine hydroxylase (TH) in carotid body (CB) glomus cells in spontaneously hypertensive rats (SHR/Izm) at 4 (prehypertensive stage), 8 (early stage of developmental hypertension), 12 (later stage of developmental hypertension), and 16weeks of age (established hypertensive stage). Age-matched Wistar Kyoto rats (WKY/Izm) were used as controls. Staining properties for TH were similar between both strains at each age. Regarding DBH immunostaining, although some glomus cells showed intense DBH immunoreactivity at 4weeks of age, these cells were rarely observed at 8, 12, and 16weeks of age in WKY/Izm. In SHR/Izm, intense DBH immunoreactivity was observed in some glomus cells at 4weeks of age, these cells were also observed at 8 and 12weeks of age, and their number increased at 16weeks of age. An image analysis showed that the percentage of DBH-immunopositive glomus cells in WKY/Izm was approximately 30% at 4weeks of age and significantly decreased to approximately 10% at 8, 12, and 16weeks of age (p<0.05). This percentage in SHR/Izm was approximately 40% at each age. The gray scale intensity for DBH immunoreactivity in DBH-immunopositive glomus cells was similar in both strains at 4weeks of age, but became significantly lower in WKY/Izm and higher in SHR/Izm with increase in age (p<0.05). These results suggest that noradrenaline in glomus cells plays an important role in the regulation of neurotransmission between CB and afferent nerves during developmental hypertension.

Protective effects of tranilast on experimental colitis in rats.

The present study aimed to verify the efficacy of tranilast (TL) for treating inflammatory bowel disease (IBD) with the use of an experimental colitis model. The experimental colitis model was prepared by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS; 40mg/kg) dissolved in water containing 25% ethanol. The pharmacological effects of TL after repeated oral administration were evaluated by biomarker and histological analyses, and the pharmacokinetic behavior of TL was also examined after single oral administration. The intrarectal instillation of TNBS solution caused colitis, as evidenced by ca. 2.2-, 5-, and 3-fold increases in myeloperoxidase (MPO) activity, infiltrated cell numbers, and the thickness of the submucosa in the colon, respectively. However, orally-taken TL (10mg/kg, twice a day for 9days) led to a 92% reduction in the increase of the MPO level by TNBS enema, and cellular infiltration and thickened submucosa in the experimental colitis model tended to also be suppressed by repeated oral administration of TL. The oral bioavailability of TL in TNBS-treated rats was calculated to be as low as ca. 6.5%, and the poor oral absorption of TL may be a limitation of the treatment for IBD. TL could attenuate TNBS-induced colitis on the basis of the obtained results, and the anti-inflammatory effects would have clinical relevance to the therapeutic outcomes of TL in IBD patients. Although further improvement in the oral bioavailability of TL might be required for better pharmacological outcomes, TL would be an efficacious agent for treating IBD.