The essential role of phospho-T38 CPI-17 in the maintenance of physiological blood pressure using genetically modified mice.

PKC-potentiated phosphorylation-dependent inhibitory protein of protein phosphatase 1 (CPI-17), an endogenous myosin phosphatase inhibitory protein, is considered a key molecule for Ca2+ sensitization of the contractile apparatus. Here, we have used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 to generate CPI-17-deficient [knockout (KO)] and threonine 38 (T38)-phospho-resistant mice [threonine mutant into alanine (TA)], and then effects of CPI-17 on vascular contractility in vitro and mean blood pressure (MBP) in vivo were investigated. In isolated thoracic aorta, phorbol 12, 13-dibutyrate induced a sustained contraction of wild-type (WT) mice, whereas no contraction showed from TA or KO mice. A high concentration of KCl solution-induced contraction was not different between transgenic and WT mice. In contrast, phenylephrine (PE)-induced contractions in both mutant strains were significantly smaller than those of WT mice in association with a low level of myosin phosphorylation, suggesting that at least part of PE-induced contraction is regulated by phosphorylation of CPI-17 at T38. Finally, the physiologic role of CPI-17 in the regulation of blood pressure was investigated using radio telemetry. MBP was decreased significantly in both transgenic mice, even with a compensatory increase in heart rate. In summary, we generated KO and constitutively phospho-resistant mouse models of CPI-17 for the first time. p-CPI-17 at T38, possibly by PKC, could be important to maintain vascular contractility and blood pressure in vivo. -Yang, Q., Fujii, W., Kaji, N., Kakuta, S., Kada, K., Kuwahara, M., Tsubone, H., Ozaki, H., Hori, M. The essential role of phospho-T38 CPI-17 in the maintenance of physiological blood pressure using genetically modified mice.

Effect of hippotherapy on gait symmetry in children with cerebral palsy: A pilot study.

We aimed to investigate the effect of hippotherapy on gait symmetry in children with cerebral palsy (CP). Twelve children with Gross Motor Function Classification System (GMFCS) levels II-IV received weekly hippotherapy lesson for 1 year. Gait analyses were performed during a 5-m walking test, using a portable, tri-axial accelerometer-based motion recorder. The baseline symmetry index derived from the Lissajous index (LI) figure before hippotherapy was greater than the LI in age-matched normal subjects (P < 0.01). Hippotherapy was associated with a decreased LI (-10.4 ± 4.9%, P = 0.018) and an improved GMFCS score (-0.6 ± 0.7, P = 0.02). These data suggest that hippotherapy has a beneficial effect on symmetry of the trunk movement in children with CP.

Evaluation of mitochondrial respiratory function in rat cardiomyocytes under different glucose conditions, using an extracellular flux analysis method.

We studied the effect of glucose supply on mitochondrial respiratory function (MRF) of neonatal rat cardiomyocytes, using a novel extracellular flux analysis. Fundamental respiratory parameters regarding oxygen consumption rate in mitochondria showed glucose concentration-dependent changes, where a significant increase or decrease in these parameters was observed to be associated with glucose concentrations ranging between 10% and 1000% of the concentration used in standard medium (3151 mg/L), respectively. By contrast, the extracellular acidification rate, a parameter of anaerobic activity, was shown to decrease under low-glucose conditions, whereas it increased after inhibiting complex V (ATP synthase) under the same glucose conditions. These findings provide a beneficial basis for various experimental studies on mitochondrial metabolism in cardiomyocytes.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 µg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator.

Electrical velocimetry for noninvasive cardiac output and stroke volume variation measurements in dogs undergoing cardiovascular surgery.

OBJECTIVE: To compare electrical velocimetry (EV) noninvasive measures of cardiac output (CO) and stroke volume variation (SVV) in dogs undergoing cardiovascular surgery with those obtained with the conventional thermodilution technique using a pulmonary artery catheter. STUDY DESIGN: Prospective experimental trial. ANIMALS: Seven adult Beagle dogs with a median weight of 13.6 kg. METHODS: Simultaneous, coupled cardiac index (CI; CO indexed to body surface area) measurements by EV (CIEV) and the reference pulmonary artery catheter thermodilution method (CIPAC) were obtained in seven sevoflurane-anaesthetized, mechanically ventilated dogs undergoing experimental open-chest cardiovascular surgery for isolated right ventricular failure. Relationships between SVV or central venous pressure (CVP) and stroke volume (SV) were analysed to estimate fluid responsiveness. Haemodynamic data were recorded intraoperatively and before and after fluid challenge. RESULTS: Bland-Altman analysis of 332 matched sets of CI data revealed an overall bias and precision of - 0.22 ± 0.52 L minute-1 m-2 for CIEV and CIPAC (percentage error: 30.4%). Trend analysis showed a concordance of 88% for CIEV. SVV showed a significant positive correlation (r2 = 0.442, p < 0.0001) with SV changes to a volume loading of 200 mL, but CVP did not (r2 = 0.0002, p = 0.94). Better prediction of SV responsiveness (rise of SV index of ≥ 10%) was observed for SVV (0.74 ± 0.09; p = 0.014) with a significant area under the receiver operating characteristic curve in comparison with CVP (0.53 ± 0.98; p = 0.78), with a cut-off value of 14.5% (60% specificity and 83% sensitivity). CONCLUSIONS AND CLINICAL RELEVANCE: In dogs undergoing cardiovascular surgery, EV provided accurate CO measurements compared with CIPAC, although its trending ability was poor. Further, SVV by EV, but not CVP, reliably predicted fluid responsiveness during mechanical ventilation in dogs.

Application of a tri-axial accelerometry-based portable motion recorder for the quantitative assessment of hippotherapy in children and adolescents with cerebral palsy.

[Purpose] This case series aims to evaluate the effects of hippotherapy on gait and balance ability of children and adolescents with cerebral palsy using quantitative parameters for physical activity. [Subjects and Methods] Three patients with gait disability as a sequela of cerebral palsy (one female and two males; age 5, 12, and 25 years old) were recruited. Participants received hippotherapy for 30 min once a week for 2 years. Gait parameters (step rate, step length, gait speed, mean acceleration, and horizontal/vertical displacement ratio) were measured using a portable motion recorder equipped with a tri-axial accelerometer attached to the waist before and after a 10-m walking test. [Results] There was a significant increase in step length between before and after a single hippotherapy session. Over the course of 2 year intervention, there was a significant increase in step rate, gait speed, step length, and mean acceleration and a significant improvement in horizontal/vertical displacement ratio. [Conclusion] The data suggest that quantitative parameters derived from a portable motion recorder can track both immediate and long-term changes in the walking ability of children and adolescents with cerebral palsy undergoing hippotherapy.

Review of studies that have used knockout mice to assess normal function of prion protein under immunological or pathophysiological stress.

Deletion of cellular isoform of prion protein (PrP(C)) increases neuronal predisposition to damage by modulating apoptosis and the negative consequences of oxidative stress. In vivo studies have demonstrated that PrP(C)-deficient mice are more prone to seizure, depression, and induction of epilepsy and experience extensive cerebral damage following ischemic challenge or viral infection. In addition, adenovirus-mediated overexpression of PrP(C) reduces brain damage in rat models of cerebral ischemia. In experimental autoimmune encephalomyelitis, PrP(C)-deficient mice reportedly have a more aggressive disease onset and less clinical improvement during the chronic phase than wild-type mice mice. In mice given oral dextran sulfate, PrP(C) has a potential protective role against inflammatory bowel disease. PrP(C)-deficient mice demonstrate significantly greater increases in blood glucose concentrations after intraperitoneal injection of glucose than wild-type mice. Further in vivo challenges to PrP gene-deficient models and conditional knockout models with siRNA and in vivo administration of PrP-ligating agents may assist in refining knowledge of the lymphoid function of PrP(C) and predicting the effects of anti-PrP treatment on the immune system. Together, these findings indicate that PrP(C) may have multiple neuroprotective and anti-inflammatory roles, which explains why this protein is so widely expressed.

Effect of Treadmill Exercise and Hydrogen-rich Water Intake on Serum Oxidative and Anti-oxidative Metabolites in Serum of Thoroughbred Horses.

The present study aimed to clarify changes of oxidative stress and antioxidative functions in treadmill-exercised Thoroughbred horses (n=5, 3 to 7 years old), using recently developed techniques for measurement of serum d-ROMs for oxidative stress, and BAP for antioxidative markers. Also, the effect of nasogastric administration of hydrogen-rich water (HW) or placebo water preceding the treadmill exercise on these parameters was examined. Each horse was subjected to a maximum level of treadmill exercise in which the horses were exhausted at an average speed of 13.2 ± 0.84 m/sec. Blood samples were taken 4 times, immediately before the intake of HW or placebo water at 30 min preceding the treadmill exercise, immediately before the exercise (pre-exercise), immediately after the exercise (post-exercise) and at 30 min following the exercise. In all horses, both d-ROMs and BAP values significantly increased at post-exercise. The increase in d-ROMs tended to be lower in the HW trial, as compared to the placebo trial at pre-exercise. The increase in BAP was considerable at approximately 150% of the pre-exercise values in both the HW and placebo treatment trials. The BAP/d-ROMs ratio was significantly elevated at post-exercise in both treatment trials, while a significant elevation was also observed at pre-exercise in the HW trial. BAP, d-ROM, and the BAP/d-ROM ratio tended to decline at 30 min after the exercise, except BAP and BAP/d-ROMs in the placebo trial. These results demonstrate that the marked elevation of oxidative stress and anitioxidative functions occurred simultaneously in the intensively exercised horses, and suggest a possibility that HW has some antioxidative efficacy.

Variation in stress resistance patterns among stx genotypes and genetic lineages of shiga toxin-producing Escherichia coli O157.

To evaluate the relationship between bacterial genotypes and stress resistance patterns, we exposed 57 strains of Shiga toxin-producing Escherichia coli (STEC) O157 to acid, freeze-thaw, heat, osmotic, oxidative, and starvation stresses. Inactivation rates were calculated in each assay and subjected to univariate and multivariate analyses, including principal component analysis (PCA) and cluster analysis. The stx genotype was determined for each strain as was the lineage-specific polymorphism assay (LSPA6) genotype. In univariate analyses, strains of the stx(1) stx(2) genotype showed greater resistance to heat than strains of the stx(1) stx(2c) genotype; moreover, strains of the stx(1) stx(2) genotype showed greater resistance to starvation than strains of the stx(2) or stx(2c) genotypes. LSPA6 lineage I (LI) strains showed greater resistance to heat and starvation than LSPA6 lineage II (LII) strains. PCA revealed a general trend that a strain with greater resistance to one type of stress tended to have greater resistance to other types of stresses. In cluster analysis, STEC O157 strains were grouped into stress-resistant, stress-sensitive, and intermediate clusters. In stx genotypes, all strains of the stx(1) stx(2) genotype were grouped with the stress-resistant cluster, whereas 72.7% (8/11) of strains of the stx(1) stx(2c) genotype grouped with the stress-sensitive cluster. In LI strains, 77.8% (14/18) of the strains were grouped with the stress-resistant cluster, whereas 64.7% (11/17) of LII strains were grouped with the stress-sensitive cluster. These results indicate that the genotypes of STEC O157 that are frequently associated with human illness, i.e., LI or the stx(1) stx(2) genotype, have greater multiple stress resistance than do strains of other genotypes.

Intracerebroventricular administration of taurine impairs learning and memory in rats.

OBJECTIVES: Taurine is a semi-essential amino acid widely distributed in the body and we take in it from a wide range of nutritive-tonic drinks to improve health. To date, we have elucidated that oral supplementation of taurine does not affect learning and memory in the rat. However, there are few studies concerning the direct effects of taurine in the brain at the behavior level. In this study, we intracerebroventricularly administered taurine to rats and aimed to elucidate the acute effects on learning and memory using the Morris water maze method. METHODS: Escape latency, swim distance, and distance to zone, which is the integral of the distance between the rats and the platform for every 0.16 seconds, were adopted as parameters of the ability of learning and memory. We also tried to evaluate the effect of intraperitoneal taurine administration. RESULTS: Escape latency, swim distance, and distance to zone were significantly longer in the intracerebroventricularly taurine-administered rats than in the saline-administered rats. Mean swimming velocity was comparable between these two groups, although the physical performance was improved by taurine administration. Probe trials showed that the manner of the rats in finding the platform was comparable. In contrast, no significant differences were found between the intraperitoneally taurine-administered rats and the saline-administered rats. DISCUSSION: These results indicate that taurine administered directly into the brain ventricle suppresses and delays the ability of learning and memory in rats. In contrast, it is implied that taurine administered peripherally was not involved in learning and memory.

Reevaluation of arrhythmias and alterations of the autonomic nervous activity induced by T-2 toxin through telemetric measurements in unrestrained rats.

This study was conducted to clarify and reevaluate the cardiac and autonomic nervous effects of T-2 toxin, which had been previously examined by several acute experiments, in unrestrained and conscious rats implanted with telemetric transmitters. Two groups of rats were given two subcutaneous injections of 0.1 and 0.5 mg/kg of T-2 toxin with an interval of 3 days. Two other groups of rat were pre-implanted with osmotic minipumps by which atropine (20 mg/kg/day) or propranolol (100 mg/kg/day) was continuously administered preceding subcutaneous injection of T-2 toxin (0.5 mg/kg). The present study demonstrated that T-2 toxin caused marked arrhythmias, such as second-degree atrioventricular (AV) block, sinus bradycardia, supraventricular extrasystole, and ventricular extrasystole, which were accompanied by a significant increase in heart rate and a significant decrease in total power and low- and high-frequency power of heart rate variability, during 3 days of observation after the toxin administration. However, the occurrence of arrhythmia with conduction disturbance such as second-degree atrioventricular blocks was markedly diminished by pretreatment with atropine, while the occurrence of ventricular extrasystole was augmented by atropine. The present study with the telemetric measurement elucidated and confirmed that T-2 toxin produced significant cardiac dysfunctions involving disturbance of the conduction pathway influenced by the autonomic nervous activity and also possible direct effects on cardiac myocytes.

Multivariate analyses revealed distinctive features differentiating human and cattle isolates of Shiga toxin-producing Escherichia coli O157 in Japan.

Genotypes of Shiga toxin-producing Escherichia coli (STEC) O157 isolated from humans and cattle were analyzed by uni- and multivariable logistic regression, and population structure methods, to gain insight into transmission and the nature of human infection. Eleven genotyping assays, including PCR typing of five virulence factors (stx(1), stx(2), stx(2c), eae, and ehxA) and a lineage-specific polymorphism assay using six markers (LSPA6), were considered in the analyses. The prevalence of the stx(1), stx(2), and stx(2c) virulence factors was significantly different between human and cattle isolates. However, multivariable regression revealed that the presence of only the stx(2) gene was significantly associated with human isolates after controlling for confounding effects. LSPA6 typing demonstrated an apparent difference in the distribution of LSPA6 lineages between human and cattle isolates and a strong association between stx genotypes and LSPA6 genotypes. Population genetics tools identified three genetically distinct clusters of STEC O157. Each cluster was characterized by stx genotypes and LSPA6 genotypes. The human isolates typically comprised LSPA6 lineage I with stx(1) stx(2) strains and LSPA6 lineage I/II with stx(2c) or stx(2) stx(2c) strains [corrected]. In contrast, the cattle isolates comprised LSPA6 lineage II strains withstx(2c) or stx(1) stx(2c) strains [corrected] in addition to the clusters identified for the human isolates. Our analyses provide new evidence that the stx(2) gene is the most distinctive feature in human isolates compared to cattle isolates in Japan, and only a subset of the genetically diverse population isolated from cattle is involved in human illnesses. Our results may contribute to international comparisons and risk assessments of STEC O157.

Abundant expression of KCNE1 in the left ventricle of the miniature pig.

Delayed rectifier potassium currents such as I (Kr) and I (Ks) play an important role in the repolarization phase of the action potential in cardiac myocytes. Electrophysiological studies have shown that the pig is a useful animal not only for clinical use as a good candidate for humans, but also for basic research in heart function or arrhythmia. However, no studies concerning the potassium channels on a molecular level have been done. To elucidate the expression level and distribution of delayed rectifier potassium channels in pigs, we quantitatively investigated the I (Kr) and I (Ks) channel subunits using the real-time polymerase chain reaction (PCR) method. The hearts from Clawn miniature pigs were separated into the apical and basal regions, and subsequently excised into transmural trisections within each of the left ventricular walls, epicardium, midcardium, and endocardium. After RNA extraction from these sites, real-time PCR was executed with reverse transcriptional products for quantitative analysis. The expression level of KCNE1 was significantly higher than those of KCNQ1, KCNH2, and KCNE2, which were comparable in all sites. Transmural heterogeneity of these potassium channel subunits was not detected on the mRNA level. These results indicate that KCNE1 is a dominant subunit on the post-transcriptional level in the miniature pig.

Identification of an ethnic-specific variant (V207M) of the KCNQ1 cardiac potassium channel gene in sudden unexplained death and implications from a knock-in mouse model.

We performed mutation analysis for genes implicated in long QT syndrome (KCNQ1, KCNH2, and SCN5A) in 17 sudden unexplained death autopsy cases. Single-strand conformation polymorphism and subsequent DNA sequencing analyses revealed that in one case, there was a variant, V207M of KCNQ1, a gene encoding a cardiac potassium channel. This case, a 40-year-old African male, was shown to have a heterozygous missense mutation (V207M), which has been previously reported to be ethnic-specific. The heterozygous V207M mutation was found in one case (0.23%) of 444 alleles from African individuals. We developed a knock-in mouse model carrier of the Kcnq1-V206M mutation, the mouse equivalent to the KCNQ1-V207M mutation identified in the victim. Significant prolongation of QT intervals was observed in the Kcnq1(V206M/V206M) mice. These findings suggest that the KCNQ1-V207M mutation might be pathogenic and might have been associated with the cause of death in the present case.

Effects of taurine on cardiovascular and autonomic nervous functions in cold exposed rats.

Exposure to cold temperature might affect on cardiovascular and autonomic nervous function. Although there are a lot of studies on physiological and pathophysiological responses of taurine, it was poorly understood the effects of taurine on cardiovascular and autonomic nervous function during cold circumstances. Therefore, the purpose of this study was to clarify the possible role of taurine on cardiovascular and autonomic nervous function in rats exposed to cold temperature. For this purpose, heart rate, blood pressure and locomotive activity were recorded from conscious and unrestrained rats using a telemetry system. Moreover, the autonomic nervous function was investigated by power spectral analysis of heart rate variability. After the recovery period of implantation of transmitter, 1% taurine was supplied during experimental period ad libitum. After the 7 days control period, both taurine administrated and control groups of rats were exposed a cold temperature. There were no differences in heart rate, blood pressure and locomotive activity between taurine and control groups before cold exposure. However, parasympathetic nervous function was somewhat predominant in taurine group. Heart rate and blood pressure in both groups increased greatly by cold exposure. Heart rate in taurine group was much higher than that in control group. LF and HF powers were decreased by cold exposure in both groups. Although no differences were observed in LF, decrease of HF in taurine group was greater than that in control group. These results suggested that taurine might provide some reservoir for cardiovascular and autonomic nervous function to cold stress in rats.

Impact of Long-Term Hippotherapy on the Walking Ability of Children With Cerebral Palsy and Quality of Life of Their Caregivers.

Background: Cerebral palsy (CP) is a permanent motor disorder that occurs at birth or during early infancy. Despite advances in fetal and maternal medicine, the incidence of CP remains high. Hippotherapy has gradually been recognized as an excellent rehabilitation tool for children with CP. However, a scientific basis for how it achieves long-term functional improvements or provides additional benefits to patients' caregivers remains unknown. Objectives: We performed a prospective trial to determine how hippotherapy affects the gross motor and gait functions in children with CP and how it may also impact the quality of life (QOL) of patients' caregivers. Methods: In total, 24 children with CP (11 boys, 13 girls; age: 4-14 years; Gross Motor Function Classification System [GMFCS] II-III) underwent a program (30 min/day, once a week) of hippotherapy or day-care recreation (control) over a 1-year intervention and a 3-month follow-up period. Assessment measures used for the children were gait parameters for a 5-m walk test, Gross Motor Function Measure (GMFM)-66, and GMFM dimension-E (GMFM-E). The QOL of the caregivers was estimated using a brief version of the World Health Organization Quality Of Life (WHOQOL-BREF) self-assessment questionnaire. Results: In addition to better GMFM-66 and GMFM-E scores, hippotherapy was associated with increased cadence, step length, and mean acceleration; stabilized horizontal/vertical displacement of patients; and better relationship between the psychological status and QOL of the caregivers than those seen in the control group (p < 0.05). Additionally, the initially improved children's step length and their caregivers' psychological QOL domain (particularly in the "positive feeling" facet) tended to be preserved up to the 3-month follow-up. Conclusion: These data suggest that compared with common day-care recreational activities, a 1-year program of once-weekly hippotherapy can improve not only the walking ability of children with CP but also the psychological health and QOL of their caregivers. Clinical Trial Registration:: www.umin.ac.jp/ctr/, identifier: UMIN000022986.

Neural anti-inflammatory action mediated by two types of acetylcholine receptors in the small intestine.

Gastrointestinal prokinetic agents function as serotonin-4 receptor (5-HT4R) agonists to activate myenteric plexus neurons to release acetylcholine (ACh), which then induce anti-inflammatory action. Details of this pathway, however, remain unknown. The aim of this study is to clarify the anti-inflammatory mechanism underlying the 5-HT4R agonist, mosapride citrate (MOS)-induced anti-inflammatory action on postoperative ileus (POI). POI models were generated from wild-type C57BL6/J (WT), 5-HT4R knock-out (S4R KO), α7 nicotinic AChR KO (α7 R KO), and M2 muscarinic ACh receptor KO (M2R KO) mice. MOS attenuated leukocyte infiltration in WT. MOS-induced anti-inflammatory action was completely abolished in both S4R KO and S4R KO mice upon wild-type bone marrow transplantation. MOS-induced anti-inflammatory action against macrophage infiltration, but not neutrophil infiltration, was attenuated in α7 R KO mice. Selective α7nAChR agonists (PNU-282987 and AR-R17779) also inhibited only macrophage infiltration in POI. MOS-mediated inhibition of neutrophil infiltration was diminished by atropine, M2AChR antagonist, methoctramine, and in M2R KO mice. Stimulation with 5-HT4R inhibits leukocyte infiltration in POI, possibly through myenteric plexus activation. Released ACh inhibited macrophage and neutrophil infiltration likely by activation of α7nAChR on macrophages and M2AChR. Thus, macrophage and neutrophil recruitment into inflamed sites is regulated by different types of AChR in the small intestine.

Effects of warm-up intensity on oxygen transport during supramaximal exercise in horses.

OBJECTIVE: To determine whether warm-up exercise at different intensities alters kinetics and total contribution of aerobic power to total metabolic power in subsequent supramaximal exercise in horses. ANIMALS: 11 horses. PROCEDURES: Horses ran at a sprint until fatigued at 115% of maximal oxygen consumption rate (VO(2max)), beginning at 10 minutes following each of 3 warm-up protocols: no warmup (NoWU), 1 minute at 70% VO(2max) (moderate-intensity warm-up [MoWU]), or 1 minute at 115% VO(2max) (high-intensity warm-up [HiWU]). Cardiopulmonary and blood gas variables were measured during exercise. RESULTS: The VO(2) was significantly higher in HiWU and MoWU than in NoWU throughout the sprint exercise period. Blood lactate accumulation rate in the first 60 seconds was significantly lower in MoWU and HiWU than in NoWU. Specific cardiac output after 60 seconds of sprint exercise was not significantly different among the 3 protocols; however, the arterial mixed-venous oxygen concentration difference was significantly higher in HiWU than in NoWU primarily because of decreased mixed-venous saturation and tension. Run time to fatigue following MoWU was significantly greater than that with NoWU, and there was no difference in time to fatigue between MoWU and HiWU. CONCLUSIONS AND CLINICAL RELEVANCE: HiWU and MoWU increased peak values for VO(2) and decreased blood lactate accumulation rate during the first minute of intense exercise, suggesting a greater use of aerobic than net anaerobic power during this period.

Impact of serial gait analyses on long-term outcome of hippotherapy in children and adolescents with cerebral palsy.

The aim of this study was to obtain data of gait parameters on predicting long-term outcome of hippotherapy. In 20 participants (4-19 years; GMFCS levels I to III) with cerebral palsy (CP), gait and balance abilities were examined after 10-m walking test using a portable motion recorder. Hippotherapy was associated with increased Gross Motor Function Measure (GMFM)-66 at 1 year from the baseline (P < 0.001). Hippotherapy increased stride length, walking speed, and mean acceleration and decreased horizontal/vertical displacement ratio over time (P < 0.05). Stride length and mean acceleration at 6 weeks predicted the elevation of GMFM-66 score. These data suggest that 1-year outcome of hippotherapy on motor and balance functions can be assessed from the early phase by serial monitoring of the gait parameters.

Phenotypic analysis of vertigo 2 Jackson mice with a Kcnq1 potassium channel mutation.

The KCNQ1 gene encodes a voltage-dependent potassium ion channel, and mutations in this gene are the most common cause of congenital long QT syndrome (LQTS). In the present study, we investigated the various phenotypic characteristics of vertigo 2 Jackson (C3H/HeJCrl-Kcnq1(vtg-2J)/J) mice with a Kcnq1 mutation. Both heterozygotes (vtg-2J/+) and homozygotes (vtg-2J/vtg-2J) showed prolonged QT intervals in electrocardiograms (ECGs) compared to C3H/HeJ control (+/+) mice. Furthermore, vtg-2J/vtg-2J mice showed gastric achlorhydria associated with elevation of their serum gastrin levels. The serum corticosterone levels were also significantly increased in vtg-2J/vtg-2J mice. In addition, vtg-2J/vtg-2J mice exhibited significantly higher blood pressure. These findings indicate that the Kcnq1 mutation in vtg-2J mice alters various physiological functions in the cardiac, gastric and adrenocortical systems, and suggest that vtg-2J mice may represent a useful model for studying Kcnq1 functions.