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.

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 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.

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.

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.

Hemodynamic changes by recombinant erythropoietin therapy in hemodialyzed patients.

Recombinant human erythropoietin therapy was given to 15 patients undergoing long-term hemodialysis with normal cardiac function. None of the patients had hypertension before the erythropoietin therapy and had received no antihypertensive agents. Before and after the erythropoietin therapy M-mode and pulsed Doppler echocardiographic studies, measurements of plasma volume by radioiodinated human serum albumin, and measurements of atrial natriuretic factor were carried out. After 6 weeks of erythropoietin therapy, hematocrit increased from 20.0 to 33.0%. Cardiac output, stroke volume, left ventricular diastolic dimensions, and left ventricular wall stress were all significantly decreased. Total peripheral resistance, interventricular septal thickness, and left ventricular posterior wall thickness were significantly increased. In Doppler echocardiographic studies, the mean velocity of aortic ejection flow and left ventricular acceleration time were decreased. The blood volume derived from plasma volume and hematocrit was not changed, whereas plasma atrial natriuretic factor concentration was significantly decreased. These data suggest that recombinant human erythropoietin administration suppressed the hyperdynamic cardiac state that was required to maintain oxygen delivery to the peripheral tissues in severe uremic anemia.

Expression of rat alpha 2-macroglobulin gene during pregnancy.

Rat alpha 2-macroglobulin (alpha 2M) is a typical acute phase protein, the concentration of which in serum increases more than 100-fold after inflammation. It is also known that the protein increases during pregnant (and neonatal) stages. Using a specific cDNA probe, expression of the alpha 2M gene during pregnancy was studied at the mRNA level. During inflammation, the liver is almost the only organ producing alpha 2M, but during pregnancy the placenta and uterus were found to be major organs producing a large amount (70-80% of that of inflamed liver) of alpha 2M mRNA at days 12-15. The yolk sac, maternal liver and fetal (or neonatal) liver also produced a small but significant amount (5-20% of that of inflamed liver) of the mRNA. Southern blotting analysis showed that only one copy of the alpha 2M gene was present in a haploid rat genome. These results indicated that a single alpha 2M gene has the ability to respond to two completely-different physiological states.

Localisation of intrahepatic interleukin 6 in patients with acute and chronic liver disease.

AIM: To evaluate the role of local interleukin 6 (IL-6) in the pathogenesis of acute and chronic liver disease. METHODS: The cellular site of IL-6 in cryostat sections of liver from 31 patients with liver disease was examined using indirect immunofluorescence with a monoclonal antibody. RESULTS: IL-6 staining in sinusoidal endothelial cells was very noticeable and diffusely distributed in the lobules of specimens of acute viral hepatitis. IL-6 expression in endothelial cells, particularly in necrotic areas of hepatocytes, was increased and was accompanied by enhanced expression in Kupffer cells. In contrast, IL-6 staining in infiltrating mononuclear cells was prominent in portal tracts, and the numbers of cytokine positive cells were greater in specimens of chronic active hepatitis compared with chronic persistent hepatitis. In non-specific reactive hepatitis intrahepatic expression of IL-6 was minimal, while in alcoholic liver fibrosis the cytokine distribution in the lobules was similar to that of acute viral hepatitis. CONCLUSIONS: These results indicate that locally produced IL-6 contributes to the inflammatory process and immunological response in acute and chronic liver disease.

Behavior of fascicles and tendinous structures of human gastrocnemius during vertical jumping.

Behavior of fascicles and tendinous structures of human gastrocnemius medialis (MG) was determined by use of ultrasonography in vivo during jumping. Eight male subjects jumped vertically without countermovement (squat jump, SQJ). Simultaneously, kinematics, kinetics, and electromyography from lower leg muscles were recorded during SQJ. During phase I (-350 to -100 ms before toe-off), muscle-tendon complex (MTC) length was almost constant. Fascicles, however, shortened by 26%, and tendinous structures were stretched by 6%, storing elastic energy of 4.9 J during phase I. During phase II (-100 ms to toe-off), although fascicles generated force quasi-isometrically, MTC shortened rapidly by 5.3%, releasing prestored elastic energy with a higher peak positive power than that of fascicles. Also, the compliance of tendinous structures in vivo was somewhat higher than that of external tendon used in the simulation studies. The results demonstrate that the compliance of tendinous structures, together with no yielding of muscle fibers, allows MTC to effectively generate relatively large power at a high joint angular velocity region during the last part of push-off.

Halo congenital nevus undergoing spontaneous regression. Involvement of T-cell immunity in involution and presence of circulating anti-nevus cell IgM antibodies.

BACKGROUND: Halo congenital nevus is a condition in which halo formation is associated with congenital nevocellular nevi. Although several theories have been proposed, the immunologic mechanisms of halo formation and concomitant nevus regression still remain unclear. We presented immunologic findings in a case of halo congenital nevus with unique histologic location of inflammatory cells. OBSERVATIONS: Histologically, the present case of halo congenital nevus undergoing spontaneous regression showed a marked inflammatory infiltrate with remnants of original nevus cell nests. In the infiltrating T cells, CD8+ cells outnumbered CD4+ cells and the infiltrate of natural killer cells was not substantial. Direct and indirect immunofluorescence studies demonstrated the presence of IgM antibodies against nevus cells as well as melanoma cells and cultured melanocytes in the patient's serum. CONCLUSIONS: Our findings suggest that both T-cell-mediated immunity and IgM antibodies may be involved in the regression of halo congenital nevus. However, it is important to point out that our results may simply be epiphenomena and not directly responsible for the destruction of nevus cells.

Glycylprolyl beta-naphthylamidase activities in serum, liver and kidney of rats in chronic carbon tetrachloride intoxication.

Following chronic carbon tetrachloride intoxication in rats, the activity of glycylprolyl beta-naphthylamidase increased in serum and decreased in liver, suggesting that the enzyme is released from liver in hepatic injury. In contrast, the enzyme activity in kidney did not decrease when the enzyme level in liver decreased significantly.

The effect of lesionectomy and the perilesional GABAergic neuronal changes in alumina cream-induced focal motor epilepsy in cats.

The effect of lesionectomy depends on the reversibility of the epileptogenic changes in the perilesional cortex. We studied how the perilesional GABAergic neuronal changes are related to the effect of lesionectomy in the alumina cream-induced focal epilepsy model in cats. Sequential changes of GABAergic neurons and spike activities were measured after the micro-injections of alumina cream (AC). Alumina granulomas were excised 15 days and 40 days after the injections. At day 20 following the AC injection, GABAergic neurons were decreased 25 to 40% compared with those in the contralateral intact cortex. At day 40, a significant increase of spike activities occurred. GABA positive cells were decreased more than 50% compared with those in the contralateral cortex. At day 80, significant cell loss in perilesional cortex was demonstrated. The effect of lesionectomy was greater in the early excised group than in the late excised group. Decrease of GABAergic neuron was more severe in the late excised group compared to the early excised group. Our results indicate that more than 50% reduction of perilesional GABA neurons may be a critical point in epileptogenesis in this model. Lesionectomy alone prior to a 50% reduction in perilesional GABAergic neurons may be sufficient for seizure control. With these data it is still unclear whether these findings contribute to the choice between lesionectomy alone and lesionectomy with resection of the perilesional cortex. Further study is needed to understand the difference between the AC epilepsy model and human chronic epilepsy.

Randomized controlled trial of twice-a-day administration of natural interferon beta for chronic hepatitis C.

We conducted a randomized controlled trial to assess the efficacy of twice-a-day administration of natural interferon beta (IFNbeta) as an induction of IFN therapy for chronic hepatitis C. Seventy-one patients with chronic hepatitis C were enrolled into the trial and randomly assigned into three treatment groups. Six million units (MU) of IFNbeta were administered once-a-day for the first 4 weeks, and then thrice weekly for 12 weeks in 20 patients (once-a-day group). Three milion units of IFNbeta were administered twice-a-day for the first 2 weeks, 6 MU once-a-day for the next 2 weeks, and then thrice weekly for 12 weeks in 23 patients (twice-a-day+beta group), or 6 MU of lymphoblastoid IFNalpha were administered thrice weekly for the last 12 weeks instead of IFNbeta in 28 patients (twice-a-day+alpha group). Four patients in once-a-day group (20%), 9 in twice-a-day+beta group (39%), and 12 in twice-a-day+alpha group (43%) obtained sustained response. Sustained response rate in twice-a-day groups was higher than in once-a-day group, although there was no statistical significance. The present study suggested the possible superiority of twice-a-day administration of IFNbeta as an induction therapy to once-a-day administration, but further studies are needed to confirm this regimen.

Correlation between occurrence of exudative epidermitis and exfoliative toxin-producing ability of Staphylococcus hyicus.

Staphylococcus hyicus was isolated from healthy pigs and pigs affected with exudative epidermitis (EE). Thirty seven strains (P-7 to P-43) were isolated from pigs affected with EE on 8 farms while 131 strains were isolated from healthy pigs bred on 2 farms in Japan. Isolation rate for pigs affected with EE was 100% while that for healthy pigs was 35.4%. The biochemical and cultural characteristics of the isolates from healthy and diseased pigs were identical except for the Voges-Proskauer reaction. The culture supernatant of many isolates caused skin exfoliation in 1-day-old chickens. Therefore, many isolates were considered to produce S. hyicus exfoliative toxin (shET). The rate of shET production by the isolates from piglets affected with EE was 87.5%, while that of the isolates from healthy pigs was 76.1%. shETs were divided in two serotypes by immunodiffusion. Piglets experimentally infected with shET-producing and nonproducing strains were observed. Local skin erythema at the inoculation site was observed with nonproducing strains and disappeared within 48 h, while the skin erythema at the sites inoculated with shET-producing strains did not disappear until 7 days after inoculation. Typical clinical signs, such as exfoliation, exudation and crusting were observed only in the piglets inoculated with shET-producing strains.

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.

Influence of acute-phase proteins on the activity of natural killer cells.

The effects of alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AGP), and haptoglobin (Hp), the main constituents of alpha-globulin and which belong to acute-phase proteins, on NK activity were examined using K562 cells as the NK target cells. Among the three proteins, alpha 1-AT and alpha 1-AGP had inhibitory effects on NK activity for "fast target" K562 cells. The alpha 1-AT preparations having the same protein concentration and a different trypsin inhibitory capacity (TIC) had an equal effect. Although alpha 1-AT and alpha 1-AGP equally reduced the NK activity, the mechanism involved in the reduction differed, in that the effect of alpha 1-AT directed toward NK cells reduced their binding capacity with the target cells. alpha 1-AGP probably interacts with a cytotoxic factor secreted from NK cells following effector-target interaction. These studies suggest that each of the acute-phase proteins, which increase following inflammation, inhibits NK cell function by two distinct mechanisms.

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.