Preparatory study of feasibility for a vertical viewing electron cyclotron emission diagnostic for the JT-60SA tokamak.

A preparatory study is underway to investigate the feasibility study of high-energetic, non-thermal electron distribution function measurements using a vertical-viewing electron cyclotron emission (ECE) diagnostic on JT-60SA. The system is designed to detect broad ECE spectra (70-260 GHz) due to the second, third, and fourth harmonics using a focusing optics system with four quasi-optical mirrors in the upper port of JT-60SA. A Gaussian beam optics design is performed in vacuum, and ray tracing calculations are performed in plasma using the TRAVIS code to investigate density characteristics. A ceramic viewing dump is also designed to reduce the effects of multiple reflections from the opposing vacuum vessel surface.

3D metal powder additive manufacturing phased array antenna for multichannel Doppler reflectometer.

Measuring the time variation of the wavenumber spectrum of turbulence is important for understanding the characteristics of high-temperature plasmas, and the application of a Doppler reflectometer with simultaneous multi-frequency sources is expected. To implement this diagnostic in future fusion devices, the use of a phased array antenna (PAA) that can scan microwave beams without moving antennas is recommended. Since the frequency-scanning waveguide leaky-wave antenna-type PAA has a complex structure, we have investigated its characteristics by modeling it with 3D metal powder additive manufacturing (AM). First, a single waveguide is fabricated to understand the characteristics of 3D AM techniques, and it is clear that there are differences in performance depending on the direction of manufacture and surface treatment. Then, a PAA is made, and it is confirmed that the beam can be emitted in any direction by frequency scanning. The plasma flow velocity can be measured by applying the 3D manufacturing PAA to plasma measurement.

Receiver circuit improvement of dual frequency-comb ka-band Doppler backscattering system in the large helical device (LHD).

Doppler-backscattering (DBS) has been used in several fusion plasma devices because it can measure the perpendicular velocity of electron density perturbation v⊥, the radial electric field Er, and the perpendicular wavenumber spectrum S(k⊥) with high wavenumber and spatial resolution. In particular, recently constructed frequency comb DBS systems enable observation of turbulent phenomena at multiple observation points in the radial direction. A dual-comb microwave DBS system has been developed for the large helical device plasma measurement. Since it is desirable to control the gain of each frequency-comb separately, a frequency-comb DBS system was developed with a function to adjust the gain of the scattered signal intensity of each channel separately. A correction processing method was also developed to correct the amplitude ratio and the phase difference between the in-phase and quadrature-phase signals of the scattered signals. As a result, the error in Doppler-shift estimation required to observe vertical velocity and the radial electric field was reduced, which enables more precise measurements.

A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.

An epidemiological survey of echinococcosis in intermediate and definitive hosts in Qinghai Province, China.

In order to understand the epidemiological status of alveolar and cystic echinococcosis in intermediate and definitive hosts in Qinghai Province, China, during the period 2007-2011, we investigated the infection in humans and animals, including yaks, Tibetan sheep, Tibetan dogs, and wild foxes distributed in different counties around the province. Sera from local residents were examined using a rapid serodiagnostic kit to detect specific antibodies against Echinococcus. Seropositive samples were confirmed with B-scan ultrasonography and X-ray examinations. Yaks and Tibetan sheep were checked at slaughterhouses, and cysts and suspicious lesions were collected for analysis. A rapid diagnostic strip was used to detect Echinococcus adults in Tibetan dogs. Positive dogs were dewormed and the parasites collected. Wild foxes were trapped and necropsies performed with particular attention to the intestine. Forty-eight of 735 (6.4%) humans tested were positive and 475 of 854 (55.6%) Tibetan sheep and 85 of 352 (24.15%) yaks were infected with Echinococcus. Across different counties, 214 of 948 (22.57%) Tibetan dogs were positive, and five of 36 (13.9%) wild foxes were infected with Echinococcus. Molecular studies showed that all the infections detected in humans, domestic yaks, and Tibetan sheep were the G1 genotype (E. granulosus), whereas the parasites from Tibetan foxes and Tibetan dogs were E. shiquicus and E. multilocularis, respectively. In conclusion, Echinococcosis is hyperendemic in Qinghai Province in both its intermediate and definitive hosts and the G1 genotype of cystic Echinococcus is the dominant strain.

Photo-induced magnetization and first-principles calculations of a two-dimensional cyanide-bridged Co-W bimetal assembly.

A two-dimensional cyanide-bridged Co-W bimetal assembly, (H5O2+)[Co(4-bromopyridine)2{W(CN)8}], was prepared. A synchrotron radiation (SR) X-ray single-crystal measurement shows that the crystal structure is monoclinic in the P21/c space group. Magnetic and spectroscopic measurements show that this assembly takes Co(S = 0)-WIV(S = 0) in the temperature range of 2-390 K. Such a wide temperature range Co-WIV phase has not been reported so far. First-principles calculations show that the band gap is composed of a WIV valence band and a CoIII conduction band. 785 nm light irradiation causes photo-induced magnetization with a Curie temperature of 27 K and a coercive field of 2000 Oe. The crystal structure of the photo-induced phase was determined to have larger lattice constants in the two-dimensional layer (bc-plane) by 3% compared to the original phase, which is due to the expansion of the distance of Co-N. The photo-induced phase returns to the original phase upon thermal treatment. First-principles calculations, and magnetic, and optical measurements prove that this photomagnetism is caused by the optical charge-transfer-induced spin transition from Co(S = 0)-WIV(S = 0) to Co(S = 3/2)-WV(S = 1/2).

Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model.

Diabetic nephropathy is the most common pathological disorder predisposing end-stage renal disease. ONO-1301 is a novel sustained-release prostacyclin analog possessing thromboxane (TX) synthase inhibitory activity. Here, we aimed to investigate the therapeutic efficacies of ONO-1301 in a rat type 1 diabetic nephropathy model. Streptozotocin (STZ)-induced diabetic rats received injections of slow-release form of ONO-1301 (SR-ONO) every 3 weeks. Animals were sacrificed at Week 14. SR-ONO significantly suppressed albuminuria, glomerular hypertrophy, mesangial matrix accumulation, glomerular accumulation of monocyte/macrophage, increase in glomerular levels of pro-fibrotic factor transforming growth factor (TGF)-beta1 and the number of glomerular alpha-smooth muscle actin (SMA)(+) cells in diabetic animals. The glomerular levels of hepatocyte growth factor (HGF) were significantly increased in SR-ONO-treated diabetic animals. Taken together, these results suggest the potential therapeutic efficacy of intermittent administration of SR-ONO in treating diabetic nephropathy potentially via inducing HGF, thus counteracting the pro-fibrotic effects of TGF-beta1.

Impact of superselective transarterial infusion therapy of high-dose cisplatin on maxillary cancer with orbital invasion.

BACKGROUND AND PURPOSE: We have been performing the superselective transarterial infusion of high-dose cisplatin for advanced maxillary cancer since 1998 and the local control rate, disease free survival rate, and organ preservation have improved markedly compared with our former therapy. This study evaluates the effectiveness of superselective transarterial infusion therapy by using high-dose cisplatin on maxillary cancer with orbital invasion. MATERIALS AND METHODS: We treated 23 patients with maxillary cancer by using superselective transarterial infusion therapy with high-dose cisplatin and concomitant radiation therapy for 10 years. Of all patients, 15 showed orbital invasion, with 11 of these tumors fed by both internal maxillary and ophthalmic arteries. In all patients, we performed superselective transarterial infusion therapy via the internal maxillary artery and/or the other feeding branches from the external carotid artery. After the operation, we determined whether a pCR had occurred by checking for the presence of viable cells. In addition, we calculated the overall survival rate, preservation rate of the eyeball, and disease-free survival rate. RESULTS: For all 23 patients, pCR and overall survival rates were 95.7% and 78.4%, respectively. To date, 2 of these patients died of lung metastasis without local recurrence. For the 15 patients with orbital invasion, the respective pCR and disease-free survival rates were 93.3% and 87.5%. Eyeballs were preserved in all patients, and local recurrence occurred in only 1 patient, at the inferior wall of the maxillary sinus (not in the orbit). CONCLUSIONS: Superselective transarterial infusion therapy with high-dose cisplatin remarkably improved the local control rate and disease-free survival rate of maxillary cancer. Even in patients with orbital invasion, a high local control rate was achieved, with preservation of the eyeball, through infusion only into branches of the external carotid artery.

Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation.

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.

Involvement of CPI-17 downregulation in the dysmotility of the colon from dextran sodium sulphate-induced experimental colitis in a mouse model.

The mechanism of gastrointestinal dysmotility in inflammatory bowel disease has not been clarified. In this study, we examined the mechanism involved in the inflamed distal colon isolated from a mouse model of dextran sodium sulphate-induced ulcerative colitis (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in the DSS-treated mouse colon. Pre-incubation with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) or the cyclooxygenase inhibitor indomethacin did not reverse the carbachol-induced contraction in the DSS-treated mouse colon. In semi-quantitative reverse transcription-polymerase chain reaction experiments and Western blot analysis, muscarinic M3 receptor expressions were not changed. The Ca2+ -sensitization of contractile elements induced by carbachol with GTP or GTPgammaS was reduced in the beta-escin-permeabilized DSS-treated mouse colon. Although the expression of proteins such as rhoA, ROCK1, ROCK2 or MYPT1 in smooth muscles was not changed, the expression of CPI-17, the functional protein involved in smooth muscle Ca2+ -sensitization, was significantly decreased in the DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in mice with colitis is attributable at least partially to the increased activity of myosin phosphatase following the downregulation of CPI-17.

A simple protocol for preventing falls and fractures in elderly individuals with musculoskeletal disease.

UNLABELLED: Our protocol resulted in a significant prevention of falls and fractures in addition to marked improvements in the balance function. Intervention comprised a new balance exercise and quadriceps femoris exercise. Subjects were outpatients aged >or=65 years old with musculoskeletal disorders who had a result of or=65 years old and had a result of

Long-lasting contractile action and the inhibitory action of cupric ions on ileal longitudinal muscle.

Cupric ions (Cu(2+)), at concentrations above 0.03 mM, induced a progressive increase in the tonic contraction of guinea-pig ileal longitudinal muscle. Maximal contraction of 0.1 mM Cu(2+) attained a level above that of the 60-mM K(+)-induced tonic response, within 20 min of application. The tension induced by Cu(2+) persisted for more than several hours. Tetrodotoxin (3 x 10(-6) M) had no effect on the contraction induced by 0.1 mM Cu(2+). After incubation in a Ca(2+)-free medium, the ileal response to 0.1 mM Cu(2+) was lost. Nifedipine, a L-type Ca(2+) channel blocker, dose-dependently inhibited contractions induced by Cu(2+). As the duration of the first application of 0.1 mM Cu(2+) increased above 30 min, after washing with normal medium, the contractile response to a second application of 0.1 mM Cu(2+) decreased gradually. After 150 min of the first application of 0.1 mM Cu(2+), a second application of Cu(2+) could not evoke any contraction. After the application of 0.1 mM Cu(2+) for 150 min, when muscles were washed with a medium containing 1 mM EDTA, the response to 0.1 mM Cu(2+) returned to a greater extent in the normal Ca(2+) medium. In conclusion, Cu(2+) (0.1 mM) induced a maximal ileal tension above that of the K-induced tonic response within 20 min. The ileal contraction to Cu(2+) persisted for more than several hours and depended on extracellular Ca(2+) concentrations. It is possible that a part of Cu(2+), bound to a EDTA-inaccessible site, also has a tension inhibitory effect.

Diurnal variation and age-related changes of bone turnover markers in female Göttingen minipigs.

We investigated diurnal variation and age-related changes in bone turnover markers in female Gottingen minipigs. Ten females, 6-9 months of age, were used for confirmation of diurnal variation. Blood was collected at 3 h intervals for 24 h, and bone-specific alkaline phosphatase and intact osteocalcin (OC) levels were determined by enzyme immunoassay and radioimmunoassay, respectively. Urine was collected at 3 h intervals for 24 h using a tray attached to the bottom of the cage. The levels of N-terminal telopeptide of type I collagen (NTX) were determined by enzyme immunoassay. Pyridinoline and deoxypyridinoline were measured by high performance liquid chromatography. OC and NTX exhibited diurnal variation (Kruskal-Wallis test, P < 0.05), with the highest and lowest levels at 18:00 h (76.7 +/- 26.2 ng/ml) and 06:00 h (44.3 +/- 10.3 ng/ml), and at 03:00-05:59 h (550.4 +/- 82.4 nmol/micromol Cr) and 12:00-14:59 h (297.8 +/- 152.5 nmol/micromol Cr), respectively. In the study of age-related changes, blood and urine samples from 66 females (age range, 3-76 months) were examined to determine the bone turnover markers. All markers showed high correlations with age (0.569 < R(2) < 0.818). High levels of bone turnover markers were observed in young animals, decreasing with age (Kruskal-Wallis test, P < 0.01). The diurnal variation and age-related changes revealed in the present study will be useful in studies of bone diseases using female Gottingen minipigs.

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

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

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

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

Beta-lactamase stability of faropenem.

Faropenem (FAR) is an orally available member of the penem class unique among carbapenems and other available beta-lactams. This study compared FAR to cephalosporins and imipenem with respect to beta-lactamase (BLA) stability and emergence of resistance to Staphylococcus aureus and Escherichia coli. BLA stability was studied using enzyme preparations from sonicated/centrifuged 24-hour cultures of E. coli, Enterobacter cloacae, Proteus vulgaris, Providencia rettgeri, Klebsiella pneumoniae, S. aureus, and Bacteroides fragilis grown in the presence of 20 mg/l ampicillin or cephaloridine to induce penicillinase or cephalosporinase, respectively. Substrate hydrolysis was quantitated spectrophotometrically. Multistep acquisition of resistance was promoted by growing bacteria in broth containing 2-fold dilutions of antibiotic over 10 cycles. Aliquots from test tubes with visible growth provided the inoculum for the next series of dilutions. FAR as well as other cephalosporins tested were highly stable to penicillinase derived from S. aureus and E. coli. However, E. coli- and P. vulgaris-derived cephalosporinase hydrolyzed cephaloridine, cefaclor and cefotiam considerably, whereas FAR was highly stable. FAR was highly stable against hydrolysis by various BLAs prepared from four B. fragilis strains and the rate of FAR hydrolysis by metallo-BLA was 5 times lower than that for imipenem. Additionally, the acquisition of resistant S. aureus strains was less pronounced for FAR compared to other agents tested. MICs rose 8-fold after the 10th sub-MIC exposure, while MICs rose 16-, 31- and 512-fold for cefixime, cefazolin and cefaclor, respectively. E. coli shifts in MICs were moderate for all the agents tested. In conclusion, FAR is characterized by pronounced BLA stability compared to other cephalosporins and imipenem. Furthermore, a lower propensity for resistance development with FAR as compared to cephalosporins was observed.

Target affinities of faropenem to and its impact on the morphology of gram-positive and gram-negative bacteria.

Faropenem is a new oral beta-lactam antibiotic unique from carbapenems and other available beta-lactams. Determinants of the in vitro activity of beta-lactam antibiotics include affinity to penicillin-binding proteins (PBPs) and beta-lactamase stability. In this study, the binding affinity of faropenem to various PBPs and its impact on the morphology of Staphylococcus aureus and Escherichia coli were evaluated. In general, faropenem demonstrated high binding affinity to high-molecular-weight PBPs but low affinity to low-molecular-weight PBPs. In S. aureus and Streptococcus pneumoniae, faropenem exhibited high binding affinity to PBP1, followed by PBP3 and PBP2. In E. coli, faropenem showed the highest affinity for PBP2, followed by PBP1A, PBP1B, PBP3 and PBP4. In Proteus vulgaris, binding was highest to PBP4, followed by PBP1A, PBP2 and PBP3. In Serratia marcescens, faropenem bound preferentially to PBP2 and PBP4. Exposure of S. aureus to faropenem at minimum inhibitory concentrations (MICs) of 1/8 or 1/4 resulted in irregular septum formation. At 1x MIC or higher, a larger number of lysed cells were observed. Exposure of E. coli to 1/8x MIC or 1/4x MIC also induced changes in cellular shape; the normal rod-shaped form changed to a spherical form in a time-dependent manner. After exposure of E. coli to 1x MIC for 2 h, bulging-shaped E. coli cells were observed and after 4 h of exposure cell lysis was demonstrated. In the presence of 4x MIC, spheroplast-like forms and cell lysis were observed. The morphological changes triggered by faropenem are in agreement with the PBP binding affinities reported. Thus, the high binding affinities of faropenem to PBPs from gram-negative and gram-positive bacteria are mirrored by its pronounced and concentration-dependent bactericidal effect.

Isolation of Pasteurella multocida during an outbreak of infectious septicemia in Japanese quail (Coturnix coturnix japonica).

In May 1994, about fifty Japanese quails out of ninety being bred for experimental purposes at Miyazaki University died of acute septicemia within a few days. At autopsy, there were no gross pathological lesions, however, severe bacteremia was observed in all cases. Bacterial examination revealed the presence of Pasteurella multocida in blood and several organs in pure culture and they were of Carter's capsular type A, Heddleston's type 3-4 and Namioka's type O-8-9. The LD50 of bacteria in quails and mice were 4.3 x 10(4) cfu and 3.9 x 10(2) cfu, respectively. All of the three chickens experimentally infected with 4 x 10(4) of the isolate died within 20 hr after the infection and several bacteria were recovered from their blood and organs. This, to our knowledge, is the first report on an outbreak of fowl cholera in Japanese quails in Japan.

Intracellular Ca2+ signaling pathway is involved in light-induced phase advance, but may not be in phase delay, of the circadian melatonin rhythm in chick pineal cell.

Chick pineal cells have photoreceptive, circadian clock and melatonin synthetic capacities, and express circadian oscillation of melatonin release in vitro. Light pulses cause phase-dependent phase shift of the melatonin rhythm. The purpose of this study was to address the questions whether intracellular calcium is involved in both light-induced phase advance and delay. Thapsigargin and cyclopiazonic acid, which deplete the intracellular calcium stores, blocked the light-induced phase advance in a dose-dependent manner. The pulses of ryanodine receptor antagonist (dantrolene sodium or ruthenium red) also blocked the light-induced phase advance. Most agents did not cause a significant phase shift by themselves. On the other hand, all the agents used, failed to block the light-induced phase delay, even if the magnitude of phase delay was decreased using low intensity light. An antagonist of nitric oxide synthase blocked neither light-induced phase advance nor phase delay. These results indicate the following possibilities: (1) the mechanism of light-induced phase advance and delay may be different in chick pineal cells, or (2) if intracellular calcium is involved in both light-induced phase advance and delay, the sensitivity to light and/or agents used in this study may differ according to Zeitgeber time.

Differential inhibitory mechanism of Fe2+ and Fe3+ on contraction of ileal longitudinal smooth muscle.

The mechanism of the inhibition of K(+)-induced contraction caused by ferrous (Fe(2+)) and ferric (Fe(3+)) ions were analysed in guinea-pig ileal longitudinal muscle and taenia coli. Fe(2+)increased the threshold for Ca(2+)-induced contraction in Ca(2+)-free, K(+)-depolarized taenia coli. However, Fe(3+)reduced the size of the maximal response to Ca(2+)without shifting the dose-response curves in taenia coli. Both 10 mM Fe(2+)and 2 mM Fe(3+)caused significant decreases in Ca uptake, as determined by the La method, during K(+)-induced ileal contraction. After treatment with 10 mM Fe(2+)in a state of cell membrane depolarization with K(+)for 30 min, the ileal K(+)-induced tonic contraction was completely restored by washing with medium containing EDTA, a chelator of divalent cations, and Fe(2+)remaining in muscle was almost eliminated by washing. In contrast, after treatment with 2 mM Fe(3+)in K(+)medium, K(+)-induced contraction was reversed only to a slight degree by washing with medium containing deferoxamine, a chelator of trivalent cations, and Fe(3+)in muscle largely remained despite the washing. These results suggest that Fe(2+)binds to the ileal surface membrane and reduces the contraction in response to K(+)mainly by inhibiting Ca(2+)influx. Fe(3+)may exert an inhibitory action on intracellular sites, in addition to the interference of Ca(2+)influx at the cell membrane.