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Functional near-infrared spectroscopy (fNIRS) can non-invasively detect hemodynamic changes associated with cerebral neural activation in human subjects. However, its signal is often affected by changes in the optical characteristics of tissues in the head other than brain. To conduct fNIRS measurements precisely and efficiently, the extraction and realtime monitoring of the cerebral functional component is crucial. We previously developed methods for extracting the cerebral functional component—the multidistance optode arrangement (MD) method and the hemodynamic modality separation (HMS) method. In this study, we implemented these methods in a software used with the fNIRS system OEG- 17APD (Spectratech, Japan), and realized a real-time display of the extracted results. When using this system for human subject experiments, the baselines obtained with the MD and HMS methods were highly stabilized, whereas originally, the fNIRS signal fluctuated significantly when the subject moved. Through a functional experiment with repetitive single-sided hand clasping tasks, the extracted signals showed distinctively higher reproducibility than that obtained in the conventional measurements.

This paper presents the results of initial physical and psycho-physical evaluations of the noise of high resolution LCDs. Five LCDs were involved, having four different pixel structures. Spatial as well as temporal noise was physically measured with the aid of a high-performance CCD camera. Human contrast sensitivity in the presence of spatial noise was determined psycho-physically using square-wave patterns stimuli as well as square stimuli. The results demonstrate that spatial noise is the dominant noise in all LCDs, while temporal noise is insignificant and plays only a minor part. The magnitude of spatial noise of LCDs is in the range between that of CRTs with a P104 and that of CRTs with a P45. Of particular importance with respect to LCD noise is the contribution of the pixel structure to the Noise Power Spectrum, which shows up as sharp spikes at spatial frequencies beyond the LCDs' Nyquist frequency. Much more work is necessary to understand the impact of spatial noise on the diagnosis of malignant abnormalities like micro-calcifications.

While most commercially available functional near-infrared spectroscopy (fNIRS) systems employ optical fibers for both the measurement optode and the transmission cable for optical signals, their material inflexibility presents some problems in stable optode fixation to the head surface and adequate cable lining to the main system. In practice, mechanical fluctuations of optical fibers in fNIRS measurement often lead to motion artifacts in the signals. A few fiberless fNIRS systems are available and equipped with light sources and detectors that directly adhere to the scalp surface. However, their shapes and detection sensitivities are not suitable for usage on a hair-covered head. Based on the commercial fiber-less fNIRS system OEG-16 (Spectratech Inc., Japan), we developed a new source-detector unit that was designed with LEDs for enhanced illumination, avalanche photodiodes instead of photodiodes, and a new holder system. The electrical circuits of the system were modified after the design. By simultaneous implementation of multidistance fNIRS measurement and hemodynamic modality separation on conventional fNIRS data at the bilateral parietal area during single-sided motor tasks, significant functional signals were observed only at the position contralateral to the side of movement. This is the first report describing a fiber-less fNIRS system that can detect functional signals on a hair-covered head. We believe this fiber-less system will improve the utility of fNIRS, particularly in less restraining conditions.

We examined the effect of KRP-297, a new thiazolidinedione derivative, on glucose uptake in the soleus muscle of two animal models of insulin resistance that show moderate (obob mice) and severe (dbdb mice) hyperglycemia. Insulin-stimulated 2-deoxyglucose (2DG) uptake in soleus muscle was 53.8% lower in obob mice versus lean mice (P < .05). When administered to obob mice, KRP-297 (0.3 to 10 mg/kg) decreased plasma glucose and insulin levels and improved the impaired insulin-stimulated 2DG uptake in soleus muscle in a dose-dependent manner. Soleus muscle from dbdb mice exhibited defects in both basal (35.0% decrease P < .01) and insulin-stimulated (50.5% decrease, P < .01) 2DG uptake. These defects were improved by treatment with KRP-297 (0.3 to 10 mg/kg). Moreover, KRP-297 prevented severe hyperglycemia and the marked decrease in pancreatic insulin content in dbdb mice. These results suggest that KRP-297 treatment is useful to prevent the development of diabetic syndromes in addition to ameliorating the impaired glucose transport in skeletal muscle.

Functional near-infrared spectroscopy (fNIRS) has been increasingly utilized for detecting human cerebral activity in many disciplines because of the potential for less-restraining conditions. However, users often suffer from motion artifacts originating from optode fluctuation during task execution when the task includes motion. In such cases, the optode fluctuation induces changes both in the reflection by hair and in the transmission between the optode and scalp. If part of the reflected light is directly received by the detector optode (short-circuited light), it will contaminate the fNIRS signal. The transmittance change at the optode–scalp gap will also contaminate the signal. In this study, we proposed an optical model on the influence of optode fluctuation on the fNIRS signal and a method for removing the influence. The model revealed the following: (1) the received short-circuited light and the gap transmittance change generated a baseline change in the detected light intensity, and (2) the signal from the tissues was downscaled with increases in the receiving intensity of short-circuited light. To avoid erroneous detection of short-circuited light, we developed a method that optically eliminated hair-reflected light from the detection using linearly polarized light sources and an orthogonally polarized analyzer. The method was validated with an optical phantom possessing a haired surface. The optical absorbance change of a close source–detector (S-D) pair equipped with polarizers was very similar to that of distant S-D pairs, even though these optodes were artificially fluctuated. By combining the multidistance optode arrangement technique with the short-circuited light elimination method, the measurement could effectively eliminate motion artifacts originating from optode fluctuation.

The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1–4 mg/kg i.v. and 5–20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1–4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of slow-reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.

1. The effects of a novel anti-asthmatic drug, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (ibudilast, KC-404) on leukotriene D4 (LTD4)-induced formation of inositol phosphates were studied in slices of guinea-pig lung and hippocampus. 2. In guinea-pig lung, ibudilast inhibited LTD4 (0.01-1 microM)-induced formation of inositol monophosphate (IP1) in a concentration-dependent manner (IC50 = 10 microM) without affecting LTD4 receptor binding. 3. Ibudilast (10 microM) inhibited histamine (0.1-1 mM)-induced formation of IP1 in guinea-pig lung slices but not in hippocampal slices. 4. Inhibition of agonist-induced formation of IP1 by ibudilast was non-competitive. 5. Ibudilast had no effect on either GTP- or calcium-stimulated phosphatidylinositol specific-phospholipase C activity of lung membranes. 6. These results suggest that ibudilast has no direct effect on LTD4 receptors, GTP binding proteins (G proteins) or phospholipase C, but inhibits inositol phosphate formation, possibly by interfering with the coupling between receptors and G proteins.

1. 1. KC-404 prevented mice from death and rats from A-V block, both induced by rapid i.v. injection of adenosine diphosphate (ADP), at high doses (5–100 mg/kg, i.v.). 2. 2. KC-404, at relatively lower doses (0.5–2 mg/kg, i.v.), inhibited the electroencephalographic (EEG) change in rat rapidly administered with arachidonic acid (AA) into the internal carotid artery. 3. 3. KC-404 (0.3–3 mg/kg, p.o.) inhibited the necrotic change of lower leg, paw or finger of rat when injected with sodium laurate into the femoral artery. 4. 4. KC-404 at doses up to 100 mg/kg, p.o. did not alter bleeding time in rat. 5. 5. Thus, KC-404 is expected to be of therapeutic value in cerebrovascular disorders accompanying thrombus in cerebral vasculature.

Possible mechanisms of the inhibitory actions of sodium nitroprusside (NaNP) on histamine-induced contractile responses of isolated rabbit aorta, basilar artery and taenia coli were studied. NaNP (3 X 10(-5) M) reduced maximum contractile response to histamine in the aorta, whereas a concentration (10(-4) M) of NaNP slightly shifted the concentration-response curve for histamine towards its higher concentrations, but did not influence the maximum response in the basilar artery and taenia coli. The reduction in the maximum response of the aorta by NaNP was reversed by removal of the endothelium, or treatment with indomethacin (5 X 10(-6) M) or quinacrine (5 X 10(-6) M), but not by nordihydroguaiaretic acid (NDGA) (5 X 10(-5) M). Prostaglandin (PG) E1, PGE2 and PGI2 produced a relaxation in histamine-contracted basilar artery and taenia coli, whereas PGE1 and PGE2 produced a weak relaxation in histamine-contracted aorta. PGD2 relaxed taenia coli contracted by histamine, but had no influences in aorta and basilar artery. From these results, it is concluded that the inhibitory action of NaNP on histamine-induced contractile response in isolated rabbit aorta may be mediated at least partly by endothelium-derived arachidonic acid metabolite(s) via the cyclooxygenase pathway which must not involve PGI2. Furthermore, the difference in the inhibitory actions of NaNP between the tissues used in this study must be attributed to the absence of such mechanisms both in the basilar artery and taenia coli.

Pharmacological action of ionophore X537A was studied in taenia coli and aortic strips isolated from rabbit. These isolated smooth muscle preparations contracted by X537A (10(-5)-10(-4) M). A removal of Ca ions from the buffer solution considerably reduced the contraction of taenia coli but not that of aorta. D 600 (methoxyverapamil, 10(-6) M) was without any effect in the contraction of both tissues by X537A (10(-4) M). However, papaverine (10(-4) M) and Aspaminol (1, 1-diphenyl-3-piperidinobutanol hydrochloride, 10(-4) M) inhibited X537A (10(-4) M)-induced contraction markedly in taenia coli but slightly in aorta. Inhibitory effects of these drugs were reversed in taenia coli by increasing Ca ion concentration in buffer solution but not in aorta. X537A (10(-4) M)-induced contraction of aorta was not affected by a pretreatment of rabbit with reserpine and preincubation of the isolated preparations with guanethidine (10(-6) M) or prazosin (10(-7) M). These results suggest that ionophore X537A might produce the contraction through an increase of Ca influx in isolated rabbit taenia coli which are little or not affected by D 600, whereas the contraction of rabbit aorta induced by X537A is mainly due to facilitation of release of Ca sequestered intracellularly.

1. 1. Verapamil caused a parallel shift of the concentration-response curve for norepinephrine in rabbit thoracic aorta and the reduction in norepinephrine-induced maximum response with shifts of the concentration-response curve for norepinephrine in renal artery and portal vein. 2. 2. Diltiazem was without any effects on the response of thoracic aorta to norepinephrine, while the responses of renal artery and portal vein to norepinephrine were inhibited noncompetitively by diltiazem. 3. 3. Verapamil but not diltiazem diminished markedly dibenamine-induced inhibition of maximum response to norepinephrine in all the preparations used. 4. 4. Specific bindings of [3H]prazosin to both the membrane fractions derived from thoracic aorta and renal artery were displaced concentration-dependently by verapamil and diltiazem, but the effective concentrations of diltiazem were more than those for Ca-entry blocking activity. 5. 5. These results suggest that verapamil might antagonize norepinephrine at α1-adrenoceptors and the effective concentration for Ca-entry blocking activity of diltiazem were less than those for the interaction of diltiazem with α1-adrenoceptors.

The effcts of sodium nitroprusside (NaNP) and diltiazem on CaCl2-, KCl- and histamine-induced contractile responses were studied in isolated rabbit basilar artery, aorta, taenia coli and trachea. NaNP reduced CaCl2-induced maximal contractions in basilar artery and aorta, but little affected those in taenia coli and trachea. NaNP reduced histamine-induced maximal contraction markedly in aorta but slightly in basilar artery and taenia coli. The reduction in aorta was reversed by increasing CaCl2 concentration in bathing medium. NaNP inhibited histamine-induced contractions of basilar artery, aorta and taeniacoli in Ca-free medium. Diltiazem reduced CaCl2-induced maximal contractions in basilar coli in Ca-free medium. Diltiazem reduced CaCl2-induced maximal contractions in basilar artery and aorta, whilst it caused a parallel shift of concentration-response curves for CaCl2 to the right in taenia coli and trachea. Diltiazem reduced histamine-induced maximal contractions in basilar artery and taenia coli. These reductions were reversed by increasing CaCl2 concentration in bathing medium. Diltiazem strongly inhibited histamine-induced contraction of taenia coli in Ca-free medium. The effects of NaNP and diltiazem on KCl-induced contractions both in normal (Ca;2.5 mM) and in high Ca (Ca;12.5 mM) media were also studied. From the results obtained in this study, the actions of NaNP and diltiazem were considered to vary with the type of smooth muscle or the condition eliciting contraction. Their possible mechanisms were discussed in this paper.

To discover the cause of the increased catecholamine levels seen in thiamine-deficiency, the relationships between the changes in tissue catecholamine level, behavior and heart rate after administration of tyramine, reserpine and amphetamine were investigated. After the injection of reserpine the catecholamine content slowly decreased in thiamine-deficient rats for 5 hours and during this time neither sedation nor change in the heart rate were observed. Amphetamine caused a greater decrease in tissue catecholamine content and more excitement in the deficient group than in the control group. The release of catecholamines caused by tyramine was similar to that caused by amphetamine; in the deficient group the release was accompanied by a marked increase in heart rate, but no behavioral changes were caused by tyramine injection in any group. The nature of the accumulated catecholamines in thiamine-deficiency is discussed with special reference to their storage and release.

1. 1. The effect of KC-404 on vertebral blood flow in the absence and presence of indomethacin was investigated in an anesthetized dog. 2. 2. KC-404 (0.2 mg/kg, i.v.) showed a significant and long lasting increase in vertebral blood flow. This was markedly diminished by pretreatment of the animal with indomethacin. 3. 3. The increase in heart rate due to KC-404 administration was also diminished, though moderately, by pretreatment with indomethacin. 4. 4. From these results, the possible mechanism of action of KC-404 was discussed, particularly in reference to cerebral vasodilating prostaglandins.

An interaction of Ca entry blockers, D600 and diltiazem, with histamine receptors was tested in rabbit aorta and basilar artery. D600 caused a parallel rightward shift of the concentration response curve for histamine. The slope values from Schild plot analysis in aorta were not different from unity. Dibenamine pretreatment caused reduction of maximum response to histamine in aorta. Such reduction was diminished markedly by the presence of D600 or chlorpheniramine in aorta but not in basilar artery. However, diltiazem did not influence the concentration response curve for histamine. These findings suggest that pharmacological property of histamine receptors in rabbit aorta is distinct from that in basilar artery. Furthermore diltiazem seems not to interact with histamine receptors in both vascular tissues.

The contractile effects of leukotrienes (LTs) C4, D4 and E4 were studied in guinea pigs isolated taenia caecum. LTs C4, D4 and E4 contracted taenia caecum at low concentrations in a concentration-dependent manner. The response to LTs was not influenced by a gamma-glutamyl transpeptidase inhibitor (L-serine borate), aminopeptidase inhibitor (L-cysteine) or cyclooxygenase inhibitor (flurbiprofen), suggesting that LTC4 and LTD4 were not metabolized or metabolized only slightly in the guinea pig isolated taenia caecum, and that each of the LTs showed the direct contractile action. Furthermore, FPL55712 antagonized the response to LTD4 and LTC4 competitively but not that to LTE4. These results suggested that the guinea pig isolated taenia caecum is useful preparation to study the pharmacological actions of LTs.

1. 1. Anti-asthmatic drug, KC-404, inhibited specifically spontaneous contraction and leukotriene (LT) D4-induced contraction of guinea-pig trachea. 2. 2. Relaxation of spontaneous contraction by KC-404 was reduced by the treatment of the guinea-pig trachea with a cyclooxygenase inhibitor, flurbiprofen. 3. 3. Some parallel shift of the concentration-action curve of LTD4 by KC-404 was still observed in the presence of flurbiprofen. 4. 4. Specific binding of [3H]LTD4 to the microsomal fraction of guinea-pig trachea was partially inhibited by KC-404. 5. 5. These results suggest that the relaxing action of trachea of KC-404 is due to the interference of interaction between LTD4 and its receptor and to the product(s) via cyclooxygenase pathway.

Pentanoylcholine iodide and n-hexyltrimethylammonium bromide were muscarinic partial agonists in a sphincter pupillae muscle of rabbit as well as intestinal smooth muscles. Both partial agonists behaved as mydriatics in a constricted pupil and as miotics in a dilated pupil.

Effects of D 600(D), diltiazem(Dil), Aspaminol(Asp), papaverine(Pap) and sodium nitroprusside(NP) were studied KCl-induced contraction: D, Dil, Asp and Pap reduced the maximal responses of the concentration-response curves in all of the tissues in normal medium (Ca,2.5mM). The reductions by Asp in aorta and by D, Dil, Asp and Pap in taenia coli were significantly reversed by increasing external Ca concentrations (Ca,12.5mM). NP little affected the contractile response in taenia coli. The reductions by NP were not affected by increasing external Ca concentrations in basilar artery and aorta Histamine-induced contraction: Maximal responses in basilar artery and taenia coli were reduced by D, Dil, Asp and Pap but not by NP, and that in aorta was reduced by Pap and NP. The reductions by NP in aorta and by Asp and Dil in taenia coli were reversed by increasing external Ca concentrations. The results of the experiments using Ca-free medium suggested that the inhibition of histamine-induced release of intracellularly sequestered Ca by D, Asp and Pap might at least contribute to the inhibitory effects of these relaxants in normal medium in basilar artery and aorta, whereas these might be mainly due to the inhibition of influx of extracellular Ca in taenia coli. Dil, only in taenia coli, and NP, only at higher concentration; in all of the tissues were also considered to inhibit the release of intracellular ly sequestered Ca. Thus, it is possible that the actions of smooth muscle relaxants vary with the difference in cellular Ca movements due to the tissue types and the conditions during development of contractions, including contractile agents and any other factors.