Effects of muscle action type on corticospinal excitability and triceps surae muscle-tendon mechanics.

This study investigated whether the specific motor control strategy reported for eccentric muscle actions is dependent on muscle mechanical behavior. Motor evoked potentials, Hoffman reflex (H-reflex), fascicle length, pennation angle, and fascicle velocity of soleus muscle were compared between isometric and two eccentric conditions. Ten volunteers performed maximal plantarflexion trials in isometric, slow eccentric (25°/s), and fast eccentric (100°/s) conditions, each in a different randomized testing session. H-reflex normalized by the preceding M wave (H/M) was depressed in both eccentric conditions compared with isometric ( P < 0.001), while no differences in fascicle length and pennation angle were found among conditions. Furthermore, although the fast eccentric condition had greater fascicle velocity than slow eccentric ( P = 0.001), there were no differences in H/M. There were no differences in motor evoked potential size between conditions, and silent period was shorter for both eccentric conditions compared with isometric ( P = 0.009). Taken together, the present results corroborate the hypothesis that the central nervous system has an unique activation strategy during eccentric muscle actions and suggest that sensory feedback does not play an important role in modulating these muscle actions. NEW & NOTEWORTHY The present study provides new insight into the motor control of eccentric muscle actions. It was demonstrated that task-dependent corticospinal excitability modulation does not seem to depend on sensory information processing. These findings support the hypothesis that the central nervous system has a unique activation strategy during eccentric muscle actions.

Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

Effect of cilostazol in preventing restenosis after carotid artery stenting using the carotid wallstent: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Restenosis after CAS is a postoperative problem, with a reported frequency of approximately 2%-8%. However differences in stent design, procedure, and the antiplatelet agent appear to affect the incidence of restenosis. We assessed the frequency of restenosis and the effect of the antiplatelet agent CLZ in preventing restenosis after CAS by the standard procedure using the CWS. MATERIALS AND METHODS: Between May 2010 and October 2011, 62 lesions in 60 consecutive patients underwent CAS using the CWS at 4 medical institutions, and all patients were followed clinically and assessed by sonography, 3D-CTA, or angiography at 3 and 6 months postoperatively. Restenosis was defined as ≥50% stenosis. The incidence of restenosis and the variation in the incidence of restenosis by the difference in type of antiplatelet agent between the CLZ group (n = 30; aspirin, 100 mg, and CLZ, 200 mg) and the non-CLZ group (n = 32; aspirin, 100 mg, and clopidogrel, 75 mg [n = 29]; or ticlopidine, 100 mg [n = 2] or 200 mg [n = 1]) were retrospectively investigated. Two antiplatelet agents were given starting 1 week preoperatively until at least 3 months postoperatively. RESULTS: Restenosis occurred in 5 patients (8.3%), but all were cases of asymptomatic lesions in the follow-up period. All 5 patients with restenosis were in the non-CLZ group, with no cases of restenosis in the CLZ group; the difference was significant (P = .0239). CONCLUSIONS: The restenosis rate after CAS by using the CWS was 8.3%. CLZ was associated with significant inhibition of restenosis.

Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function.

BACKGROUND: Recently, it has been reported that frequent premature ventricular contractions (PVCs) may be associated with causing heart failure in patients with left ventricular (LV) dysfunction. However, the prognostic significance of frequent PVCs in asymptomatic patients with a normal LV function is unclear. METHODS: Two hundred and thirty-nine consecutive patients presenting with frequent PVCs (>1000 beats/day) originating from the right or left ventricular outflow tract without any detectable heart disease were enrolled in the study. Structural heart disease was ruled out by echocardiography and cardiac magnetic resonance imaging, and Holter-ECG monitoring was repeated two or three times to evaluate the PVC prevalence at the initial evaluation. All patients were followed up for at least 4 years, and further observation was continued if possible. RESULTS: During an observation period of 5.6 (1.7) years, no patients exhibited any serious cardiac events. Although there was no significant change in the mean LV ejection fraction (LVEF) and mean LV diastolic dimension (LVDd), there was a significant negative correlation between the PVC prevalence and DeltaLVEF (p<0.001) and positive correlation between the PVC prevalence and DeltaLVDd (p<0.001). When the development of LV dysfunction was defined as DeltaLVEF>-6%, 13 patients exhibited LV dysfunction. For the prediction of the development of LV dysfunction, PVC prevalence and LVEF at the initial evaluation were independent predicting factors (p<0.01). CONCLUSION: Although the prognosis in patients with frequent PVCs was considered relatively benign, attention should be paid to the progression of the LV dysfunction during a long-term observation, especially in patients with a high PVC prevalence.

Electron transmission characteristics of Au/1,4-benzenedithiol/Au junctions.

Electron transmission through individual 1,4-benzenedithiol molecules bridging between two gold electrodes (Au/BDT/Au junctions) has been studied by measuring the current-voltage (I-V) characteristics. Measurements were made at room temperature on three junction states of conductance 0.005G(0), 0.01G(0), and 0.1G(0), respectively, where G(0) is the quantum unit of conductance. All I-V curves are linear around zero bias and nonlinearly increase upward for biases above approximately 0.2 V. Absence of plateaus in the observed I-V characteristics up to +/- 1 V indicates that the electron transmission spectrum of Au/BDT/Au has no peaks within +/- 0.5 eV from the Fermi level.

Sympathovagal effects of spinal anaesthesia with intrathecal or intravenous fentanyl assessed by heart rate variability.

BACKGROUND: Although many investigators previously reported the sympathovagal effect of spinal anaesthesia, there is no information about the sympathovagal effects of supplementation with fentanyl. The aim of this study was to evaluate the sympathovagal effects of intrathecal or intravenous fentanyl added to spinal anaesthesia. METHODS: One hundred and twenty patients undergoing elective transurethral surgery under spinal anaesthesia were randomly allocated to receive intrathecally either isobaric bupivacaine alone (Group B), bupivacaine supplemented with intrathecal (Group Ft) or with intravenous fentanyl (Group Fv). Heart rate variability was estimated using the MemCalc method (Tarawa, Suwa Trust, Japan) before and after spinal anaesthesia. RESULTS: In all groups, spinal anaesthesia significantly decreased low frequency/high frequency (LF/HF) as a marker of sympathovagal balance. However, patients in Group B with a low block height developed a marked increase in LF/HF after spinal anaesthesia, which was attenuated in Group Ft. Meanwhile, intravenous fentanyl did not attenuate this response. CONCLUSION: We conclude that sympathetic activation observed in patients with a low block height was attenuated by intrathecal fentanyl but not by intravenous fentanyl.

Effects of KP-496, a novel dual antagonist of leukotriene D(4) and thromboxane A (2) receptors on nasal blockage in guinea pig models of allergic rhinitis.

OBJECTIVE AND DESIGN: KP-496 is a novel dual antagonist for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors. We investigated effects of KP-496 on antigeninduced nasal blockage in 2 guinea pig models of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Animals were actively sensitized with ovalbumin (OVA) or Japanese cedar pollen, and were then repeatedly challenged with OVA or pollen, respectively. KP-496 (0.003 %-0.05 %) was intranasally administered 0.5 or 1 h before and 2 h after an antigen challenge. METHODS: As an indicator of nasal blockage, specific airway resistance was measured using a double-flow plethysmograph system. Statistical analyses were performed with Dunnett's test (OVA model) or t-test (pollen model). RESULTS: Although early phase response was not affected by even a high dose (0.03 %) of KP-496, late phase nasal blockage (1.68 +/- 0.26) was inhibited by 0.01 % (0.87 +/- 0.19; p <0.05) and 0.03 % (0.44 +/- 0.12; p <0.01) of KP-496 in the OVA model. On the other hand, both early (5.60 +/- 0.77) and late phase responses (7.90 +/- 1.70) were inhibited by 0.05 % KP-496 to 2.68 +/- 0.84 (p <0.05) and 2.71 +/- 0.83 (p <0.05), respectively, in the pollen model, in which nasal hyperresponsiveness had been acquired by multiple challenges. CONCLUSIONS: KP-496 may be clinically effective for nasal blockage in allergic rhinitis.

Transcutaneous electrical nerve stimulation at the PC-5 and PC-6 acupoints reduced the severity of hypotension after spinal anaesthesia in patients undergoing Caesarean section.

BACKGROUND: Despite prophylactic measures, hypotension remains a common side-effect of spinal anaesthesia for parturients. Electroacupuncture at the Neiguan (PC-6) and Jianshi (PC-5) points influences haemodynamics. We thus hypothesized that transcutaneous electrical nerve stimulation (TENS) at traditionally used acupuncture points would reduce the severity of hypotension after spinal anaesthesia in patients undergoing Caesarean section. METHODS: After obtaining approval from the local ethics committee and written informed patient consent, 36 singleton parturients undergoing Caesarean section under spinal anaesthesia were randomized into three groups. The control group received no treatment, and the acupoint and non-acupoint groups received TENS at the PC-5 and PC-6 points of both arms and non-acupoints of both shoulders, respectively. RESULTS: The median (range) of the lowest recorded systolic blood pressure was significantly higher in the acupoint group compared with the other groups and that of the non-acupoint group was higher than that of the control group [control, 70 (68-82) mm Hg; acupoint, 94 (84-109) mm Hg; non-acupoint, 81 (70-92) mm Hg: P<0.001]. Significantly more parturients in the control and non-acupoint groups experienced hypotension [control, 10 (83%); acupoint, 4 (33%); non-acupoint, 10 (83%): P=0.013]. More ephedrine was required to maintain arterial blood pressure in the control and non-acupoint groups. CONCLUSIONS: TENS on the traditional acupuncture points reduced the severity and incidence of hypotension after spinal anaesthesia in parturients.

Effects of KP-496, a novel dual antagonist at the cysteinyl leukotriene receptor 1 and the thromboxane A(2) receptor, on airway obstruction in guinea pigs.

BACKGROUND AND PURPOSE: KP-496 is a novel dual antagonist for cysteinyl leukotriene receptor 1 (CysLT(1)) and thromboxane A(2) (TXA(2)) receptor (TP). The aim of this study was to evaluate the pharmacological profile of inhaled KP-496 and its effects on airway obstruction. EXPERIMENTAL APPROACH: Antagonist activities of inhaled KP-496 were investigated using bronchoconstriction induced in guinea pigs by LTD(4) or U46619, a stable TXA(2) mimetic. Guinea pigs sensitized with injections of ovalbumin were used to assess the effects of inhaled KP-496 on bronchoconstriction induced by antigen (i.v.). Another set of guinea pigs were sensitized and challenged with ovalbumin by inhalation and the effects of inhaled KP-496 on immediate and late airway responses and airway hyperresponsiveness were investigated. KEY RESULTS: KP-496 significantly inhibited LTD(4)- and U46619-induced bronchoconstriction in a dose-dependent manner. The inhibitory effects of KP-496 (1%) were comparable to those of montelukast (a CysLT(1) antagonist, p.o., 0.3 mg kg(-1)) or seratrodast (a TP antagonist, p.o., 3 mg kg(-1)). KP-496 (1%) and oral co-administration of montelukast (10 mg kg(-1)) and seratrodast (20 mg kg(-1)) significantly inhibited antigen-induced bronchoconstriction, whereas administration of montelukast or seratrodast separately did not inhibit antigen-induced bronchoconstriction. KP-496 exhibited dose-dependent and significant inhibitory effects on the immediate and late airway responses and airway hyperresponsiveness following antigen challenge. CONCLUSIONS AND IMPLICATIONS: KP-496 exerts effects in guinea pigs which could be beneficial in asthma. These effects of KP-496 were greater than those of a CysLT(1) antagonist or a TP antagonist, in preventing antigen-induced airway obstruction.

Parental presence during induction enhances the effect of oral midazolam on emergence behavior of children undergoing general anesthesia.

BACKGROUND: Pre-anesthetic anxiety and emergence agitation are major challenges for anesthesiologists in pediatric anesthesia. Thus, sedative premedication and parental presence during induction of anesthesia (PPIA) are used to treat pre-anesthetic anxiety in children. The aim of the present study was to test if a combination of mother presence and midazolam premedication is effective for improving emergence condition in children undergoing general anesthesia. METHODS: Sixty children were allocated to one of three groups: a sedative group (0.5 mg/kg oral midazolam), a PPIA group or a sedative and PPIA group. When anesthesia was induced with 7% sevoflurane in 100% oxygen, qualities of mask induction were rated. Anesthesia was maintained with sevoflurane (1.5-2.5%) in 60% oxygen and intravenous fentanyl 4 microg/kg. During emergence from anesthesia, the score of the child's emergence behavior was rated. RESULTS: The children in the midazolam group showed a better quality of mask induction compared with those in the PPIA group, the addition of parental presence to oral midazolam did not provide additional improvement of mask induction. In contrast, the children in the midazolam + PPIA group were less agitated than those in the other groups at emergence from anesthesia. CONCLUSION: Parental presence during induction of anesthesia enhanced the effect of oral midazolam on emergence behavior of children undergoing general anesthesia.

Correlation between heart rate variability and haemodynamic fluctuation during induction of general anaesthesia: comparison between linear and non-linear analysis.

The objective of this study was to compare linear and non-linear analysis of heart rate variability (HRV) in terms of correlation with haemodynamic fluctuation during induction of general anaesthesia. Pre-operatively, HRV was estimated by the MemCalc method in 114 patients scheduled for general anaesthesia. After anaesthesia was induced with propofol, fentanyl and vecuronium bromide, tracheal intubation was performed. Haemodynamic fluctuations during induction of anaesthesia were recorded and the correlation between pre-operative HRV and haemodynamic fluctuation was examined using logistic regression analysis. As an index of non-linear analysis of HRV, ultra short-term entropy (UsEn) correlated better with blood pressure fluctuation than did the ratio of the power of low frequency component of HRV to that of high frequency component (LF/HF). In contrast, although LF/HF significantly correlated with heart rate increase caused by tracheal intubation, the correlation between UsEn and heart rate fluctuation was not significant.

Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers.

BACKGROUND AND AIMS: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. METHODS: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. RESULTS: cDNA array revealed that matrilysin was maximally upregulated in the metastasis signature identified. Tumour matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between matrilysin and nodal metastasis. CONCLUSIONS: We have provided evidence that tumour matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.

Molecular and morphological differentiation between the crop and weedy types in velvetleaf (Abutilon theophrasti Medik.) using a chloroplast DNA marker: seed source of the present invasive velvetleaf in Japan.

A comparison of chloroplast DNA (cpDNA) sequences was carried out between the crop and weed types of Abutilon theophrasti to clarify the seed source of the present weedy velvetleaf in Japan. A sequencing analysis of approx. 6% of the chloroplast genome (ca 10 kbp) detected three nucleotide substitutions, one six-base-pair insertion/deletion (indel) and one 30-base pair inversion, which distinguish two haplotypes of cpDNA. A PCR-based survey of the indel and the inversion revealed that the 93 accessions of velvetleaf collected from the world could be divided into two groups. A morphological marker (capsule color) could be used to discriminate the crop type and the weed type, and hence, along with cpDNA haplotype, to distinguish three genotypes (Type I, II, and III). All Japanese cultivars and crop accessions from other countries were Type I. Weed types were divided into Type II and III. All of the samples from the USA, and the samples taken from grain imports to Japan were Type III. Since most of the weedy types distributed in Japan were of Type III, it is argued that they were introduced as seeds in the imported grain. We also found that the Type II plants sporadically occurred in Japan. It is suggested that they originated as hybrids, with indigenous cultivars as the maternal ancestor. Such hybrids must have survived since the cessation of velvetleaf cultivation about a century ago.

Photoelectron trapping in quadrupole and sextupole magnetic fields.

A photoelectron-trapping phenomenon has been found in the simulation of the photoelectron cloud. It is found that the photoelectrons can be trapped in the quadrupole and sextupole magnetic fields for very long time until it longitudinally drifts out of the magnets, even a long bunch train separation is not sufficient to clear up the photoelectrons. Therefore, such a kind of long time trapped photoelectron cloud can cause coupled bunch instability. The trapping phenomenon is strongly beam dependent, especially on the bunch length. There is no such kind of trapping if the positron beam does not disturb the photoelectrons during the whole process. There is also no trapping for positron bunch with bunch length longer than the period of the photoelectron's gyration motion at the mirror points. The trapping is a mirror field trap which is caused by beam disturbance. The trapping phenomenon and mechanism will be presented in detail.

Effects of risperidone, an atypical antipsychotic drug, on excitatory synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

The effects of an atypical antipsychotic drug, risperidone, were examined on excitatory synaptic responses in the dentate gyrus by single electrical stimulations to the perforant path and the induction of long-term potentiation (LTP) in this pathway in chronically prepared rabbits. Any of 0.5, 1.0 and 2.0 mg/kg doses of risperidone intraperitoneally injected had virtually no effect on the excitatory synaptic responses. However, these three doses of risperidone dose-dependently suppressed the LTP induction.

Usefulness of BMIPP SPECT to evaluate myocardial viability, contractile reserve and coronary stenotic progression after reperfusion in acute myocardial infarction.

Using combined 123I-BMIPP (BMIPP), 201Tl (Tl) and 99mTc-PYP (PYP) myocardial SPECT imaging, risk areas of acute myocardial infarction were documented in the acute stage, and then these images were evaluated for how well they reflected muscle viability, contractile reserve and coronary stenotic progression subsequent to reperfusion therapy. Patients who only experienced a first attack of myocardial infarction were enrolled. In total, 36 cases who had had the occluded artery successfully reperfused were examined during the past year. They had no significant vessel disease except for the culprit single artery. The patients were comprised of 32 men and 4 women. The mean age was 59.5 years. All patients underwent coronary angiography and left ventricular (LV) angiography in the emergency room. BMIPP/Tl and PYP myocardial SPECT were conducted in the acute stage and chronic stage. In the chronic stage LV angiography was repeated to assess the improvement of LV wall motion. The response to postextrasystolic potentiation (PESP) testing was performed to estimate myocardial contractile reserve. The risk area of acute myocardial infarction (AMI) was documented by reduced BMIPP accumulation. The size of reduced BMIPP accumulation was larger than that of PYP accumulation. A BMIPP/Tl discrepancy and PYP accumulation were documented to assess myocardial viability. Both improvement in LV wall motion and augmentation of PESP response were more closely related to a BMIPP/Tl discrepancy in the presence or absence of PYP accumulation. Therefore, it would be possible to evaluate myocardial viability and contractile reserve by the BMIPP/Tl discrepancy. In patients with good viability, it is important to predict whether there is coronary stenotic progression or not. In this study, we demonstrated that most patients with improved BMIPP images had no significant progression at the site of intervention. Serial observation of BMIPP images from the acute stage to the chronic stage might enable us to predict the progression of coronary stenosis.

[Clinical evaluation of urinary nuclear matrix protein 22 as a marker for bladder cancer].

The purpose of this study is to evaluate the clinical usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for bladder cancer. We examined the positive rates of NMP22 test, urinary cytology and bladder tumor antigen (BTA) test, and compared the positive rate of NMP22 test with that in urinary cytology and BTA test. Urine samples were obtained from 50 patients with histologically confirmed bladder cancer before the treatment. The samples were examined by NMP22 test, urinary cytology and BTA test. In 50 patients with bladder cancer, the overall positive rate was 40% for NMP22 test, 40% for urinary cytology, and 16% for BTA test. A combination of NMP22 test and urinary cytology showed a significantly higher positive rate (54%) as compared to NMP22 test or urinary cytology alone. When NMP22 test and urinary cytology were compared for tumor size, number, shape, stage and grade, NMP22 test showed a significant higher positive rate than urinary cytology in grade 1 bladder cancer. In conclusion, although NMP22 test and urinary cytology gave a similar positive rate, a combination of NMP22 test and urinary cytology is more useful than the NMP22 test or urinary cytology alone for monitoring of bladder cancer.