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Biomedical subjects

H Araki

Publications and source records attributed to H Araki.

At least 109 records · Page 6Linked to original sources
PubMed1998

Involvement of the central catecholaminergic system in nicotine-induced tail-tremor in rats.

The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day, subcutaneously) became more pronounced in intensity with daily administration for 9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms, intracerebroventricularly) showed almost the maximum degree of tail-tremor during the whole experimental period. However, in rats pretreated with 6-hydroxydopamine plus desipramine, enhancement of tail-tremor was slight in the beginning but increased with the daily nicotine administration. Fourteen-day administration of nicotine did not result in significant changes in noradrenaline and dopamine levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results suggest that nicotine-induced tail-tremor is associated with the supersensitivity of postsynaptic catecholaminergic receptors in the central nervous system, and that the noradrenergic system may be more important than the dopaminergic system in this phenomenon.

Animals↗
PubMed1998

Cyclooxygenase-2 selective and nitric oxide-releasing nonsteroidal anti-inflammatory drugs and gastric mucosal responses.

Occurrence of gastrointestinal damage and delayed healing of pre-existing ulcer are commonly observed in association with clinical use of nonsteroidal antiinflammatory drugs (NSAIDs). We examined the effects of NS-398, the cyclooxygenase (COX)-2 selective inhibitor, and nitric oxide (NO)- releasing aspirin (NCX-4016) on gastric mucosal ulcerogenic and healing responses in experimental animals, in comparison with those of nonselective COX inhibitors such as indomethacin and aspirin. Indomethacin and aspirin given orally were ulcerogenic by themselves in rat stomachs, while either NS-398 or NCX-4016 was not ulcerogenic at the doses which exert the equipotent antiinflammatory action with indomethacin or aspirin. Among these NSAIDs, only NCX-4016 showed a dose-dependent protection against gastric lesions induced by HCl/ethanol in rats. On the other hand, the healing of gastric ulcers induced in mice by thermal-cauterization was significantly delayed by repeated administration of these NSAIDs for more than 7 days, except NCX-4016. Gastric mucosal prostaglandin contents were reduced by indomethacin, aspirin and NCX-4016 in both normal and ulcerated mucosa, while NS-398 significantly decreased prostaglandin generation only in the ulcerated mucosa. Oral administration of NCX-4016 in pylorus-ligated rats and mice increased the levels of NO metabolites in the gastric contents. In addition, both NS-398 and NCX-4016 showed an equipotent anti-inflammatory effect against carrageenan-induced paw edema in rats as compared with indomethacin and aspirin. These results suggest that both indomethacin and aspirin are ulcerogenic by themselves and impair the healing of pre-existing gastric ulcers as well. The former action is due to inhibition of COX-1, while the latter effect may be accounted for by inhibition of COX-2 and mimicked by NS-398, the COX-2 selective NSAID. NCX-4016, despite inhibiting both COX-1 and COX-2, protects the stomach against damage and preserves the healing response of gastric ulcers, probably because of the beneficial action of NO.

Animals↗
PubMed1998

Angiotensin inhibits neurotransmission of calcitonin gene-related peptide-containing vasodilator nerves in mesenteric artery of spontaneously hypertensive rats.

The role of angiotensin (Ang) in neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) (8- and 15-week-old) and age-matched Wistar Kyoto rats (WKY) was investigated. In both SHR and WKY preparations precontracted by continuous perfusion of Krebs' solution containing 7 microM methoxamine plus 5 microM guanethidine, periarterial nerve stimulation (PNS; 1 and 2 Hz) produced a frequency-dependent vasodilation, which was abolished by 100 nM tetrodotoxin and 500 nM CGRP(8-37) (CGRP receptor antagonist). The PNS-induced vasodilation in the SHR decreased with age and was smaller than that in the WKY. The neurogenic vasodilation in the SHR but not WKY was significantly inhibited by N-acetyltetradecapeptide renin substrate (RS, 100 and 500 nM), AngI (50 and 100 nM) and AngII (50 and 100 nM). The inhibitory effects of RS, AngI and AngII were abolished by the AngII receptor antagonist, [Sar1,Ile8]AngII (500 nM). The effect of RS and AngI was inhibited by captopril (5 microM) and temocapril (500 nM). AngII (100 nM) had no effect on vasodilator response to exogenously infused CGRP (100 pmol). PNS (2 Hz) of perfused mesenteric vascular beds increased the release of CGRP-like immunoreactivities (CGRP-LI) in the perfusate, which was less in 15-week-old SHR than in age-matched WKY. AngII (100 nM) significantly inhibited the neurogenic release of CGRP-LI in the SHR but not in the WKY. These results suggest that exogenous and locally converted AngII, via AngII receptors, modulates the neurotransmission of CGRP-containing vasodilator nerves by inhibiting CGRP release from the nerve.

Angiotensin I↗
PubMed1998

[Detection of apolipoproteins E5 and E7 by a widely used commercial ApoE IFE kit--evidence provided by genotyping].

The purpose of this study is to examine a possibility to detect apolipoprotein (apo) E5 and E7 isoproteins with a commercial kit widely used (Phenotyping Apo E IFE System, Jokoh Co. LTD., Tokyo) and to clarify the frequency of the rare alleles in Central Japan. A total of 1,445 subjects living in Central Japan (1,030 hemodialysis patients and 415 apparently healthy individuals) was phenotyped for apo E isoproteins with the kit using isoelectric focusing with immunoblotting. In 23 subjects, unique apo E4 isoproteins, which migrate more basically than apo E4 isoprotein, were found. These unique isoproteins were proved to be apo E5 or E7 isoproteins by PCR with restriction fragment length polymorphism and with amplification refractory mutation systems, respectively. No significant differences in the frequencies of apo E5 or apo E7 alleles were observed between healthy individuals and hemodialysis patients (0.011 vs. 0.018, NS). The frequencies of apo E5 and E7 alleles were 0.001 and 0.005, respectively, in healthy individuals, and 0.003 and 0.005, respectively, in hemodialysis patients. These data in Central Japan were consistent with those in Western Japan (Matsunaga, et al, Clin Genet, 1995). These results indicate that the commercial kit is applicable to detect the rare alleles, apo E5 and E7 alleles and that the frequencies of the rare alleles in Central Japan are similar to those in Western Japan.

Adult↗
PubMed1998

[Radiotherapy for carcinoma of the buccal mucosa: analysis of prognostic factors].

The radiotherapeutic results of 55 patients with carcinoma of the buccal mucosa were analyzed to determine the prognostic factors and appropriate treatment modality. They were classified into 5 groups according to treatment modality: group A (preoperative radiotherapy followed by surgery), group B (interstitial implant), group C (electron therapy), group D (mainly external radiotherapy) and group E (external radiotherapy followed by mold therapy with remote afterloading system). The overall 5-year survival rates for groups A, B, C, D, E and the entire group were 50%, 61%, 67%, 29%, 25% and 48%, respectively. The cumulative 5-year local control rates for groups A through E were 81%, 94%, 75%, 33% and 25%, respectively. In univariate analysis, T stage (T1-2 vs. T3-4), N stage (N0 vs. N1-3), clinical stage (II vs. III-IV), histologic grade (well differentiated vs. moderately and poorly differentiated) and treatment modality (A-C vs. D-E) were significantly related to overall survival (p < 0.05). Multivariate analysis revealed that treatment modality (groups A-C) and N0 stage were significantly associated with favorable prognosis (p < 0.05). These results suggest that interstitial implants are comparable with surgery for T1 to early T3 lesions, with or without slight invasion to the bucco-alveolar sulci or retromolar areas, that can be treated with a single-plane implant.

Adult↗
PubMed1997

Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils.

TTC-909 (Clinprost), a chemically stable PGI2 analog, isocarbacyclin methyl ester (TEI-9090 or Clinprost) incorporated in lipid microspheres, when administered intravenously after brain ischemia, prevents ischemic neuronal damage possibly by modulating cerebral blood flow and platelet aggregation. However, the possibility exists that TEI-7165, which is the free acid form and a central metabolite of TEI-9090, has direct neurotrophic action in vivo, since TEI-7165 has been shown to block neuronal voltage-dependent Ca2+ channels in vitro, and a novel prostacyclin receptor showing high affinity with TEI-7165 has been detected in a variety of brain regions including the hippocampus. In the present study, we infused TEI-7165 for 7 days into the lateral ventricle of gerbils starting 2 h before or just after 3-min forebrain ischemia. TEI-7165 infusion prevented significantly the ischemia-induced shortening of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region, as well as synapses within the strata moleculare, radiatum and oriens of the region, were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. TEI-7165 infusion did not affect hippocampal blood flow or temperature. These findings, together with the previously depicted accumulation of centrally administered [3H]TEI-7165 around hippocampal neurons, suggest that TEI-7165 has a direct neuroprotective action in brain ischemia.

Animals↗
PubMed1997

Vasodilation profile of CD-832, a novel dihydropyridine derivative in rabbit aorta.

1. CD-832, nifedipine and nitrendipine, but not nitroglycerin and nicorandil, inhibited the KCl-induced contraction of rabbit aortas. 2. CD-832, nitroglycerin and nicorandil, but not nifedipine and nitrendipine, inhibited the norepinephrine-induced contraction of aortas. The inhibitory effects of these agents were either potentiated or inhibited by zaprinast or methylene blue, respectively. 3. On the KCl-induced contraction, the duration of CD-832-induced vasodilation was longer than that of nifedipine. Concerning the norepinephrine-induced contraction, the duration of CD-832-induced vasodilation was longer than that of nicorandil. 4. These results suggest that the mechanism of CD-832-induced vasodilation concerns both Ca(2+)-antagonistic action and a nitratelike action. Furthermore, the vasodilation is long lasting.

Adrenergic alpha-Agonists↗
PubMed1997

Bottleneck effect on evolutionary rate in the nearly neutral mutation model.

Variances of evolutionary rates among lineages in some proteins are larger than those expected from simple Poisson processes. This phenomenon is called overdispersion of the molecular clock. If population size N is constant, the overdispersion is observed only in a limited range of 2N sigma under the nearly neutral mutation model, where sigma represents the standard deviation of selection coefficients of new mutants. In this paper, we investigated effects of changing population size on the evolutionary rate by computer simulations assuming the nearly neutral mutation model. The size was changed cyclically between two numbers, N1 and N2 (N1 > N2), in the simulations. The overdispersion is observed if 2N2 sigma is less than two and the state of reduced size (bottleneck state) continues for more than approximately 0.1/u generations, where u is the mutation rate. The overdispersion results mainly because the average fitnesses of only a portion of populations go down when the population size is reduced and only in these populations subsequent advantageous substitutions occur after the population size becomes large. Since the fitness reduction after the bottleneck is stochastic, acceleration of the evolutionary rate does not necessarily occur uniformly among loci. From these results, we argue that the nearly neutral mutation model is a candidate mechanism to explain the overdispersed molecular clock.

Biological Evolution↗
PubMed1997

Application of muscle microdialysis to evaluate the concentrations of the fluoroquinolones pazufloxacin and ofloxacin in the tissue interstitial fluids of rats.

Muscle microdialysis has been used to determine the unbound concentrations of the fluoroquinolones, pazufloxacin and ofloxacin, in tissue interstitial fluids (Cisf,u) of rats under steady state conditions. Cisf,u was estimated from the concentration in dialysate and the in-vitro permeability rate constant by the extrapolation method based on the clearance concept. Paper-disks were inserted under the abdominal skin of rats, and the drug concentrations in the fluids penetrating into the disks (Cdisk) were measured and compared with Cisf,u. The Cisf,u of pazufloxacin and ofloxacin in muscle were close to their unbound concentrations in the venous plasma; these were 75.3% and 77.1%, respectively, of the total concentrations in plasma at the steady state. The Cdisk of pazufloxacin and ofloxacin were also close to their Cisf,u. These results indicate that the unbound concentrations of the fluoroquinolones in the tissue interstitial fluids were the same as those in the venous plasma. The disk insertion technique seems to be useful for evaluating drug concentrations in tissue interstitial fluid.

Animals↗
PubMed1997

T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use.

Animals↗
PubMed1997

Prolonged arterial occlusion caused by thrombus development at sites of arterial bifurcation.

Although thrombogenic atheromas frequently develop at sites of arterial branching or bifurcation, the nature of such thrombus formation remains unclear. In this study, small rat mesenteric arteries (about 0.3 mm id) were observed using a video-microscope system. Exposure of the media by inducing compression damage over a short segment caused occlusive thrombus formation and subsequent spontaneous reperfusion repeatedly over about 30 min. Compression damage was induced either at a site just distal to the bifurcation (group 1, n = 7) or 5-10 mm downstream from the bifurcation (group 2, n = 7). The number of thrombotic occlusions was similar in the 2 groups, but the total duration of occlusion was significantly higher in group 1 (540 +/- 47 sec) than in group 2 (295 +/- 24 sec) (p < 0.01). The total duration of occlusion in group 1 was significantly reduced to 273 +/- 16 sec (p < 0.01) by mechanical interruption of flow in the other, intact, arterial branch. In the presence of blood flow through the intact branch, the occlusive thrombus at the bifurcation further enlarged in the direction of the intact branch, resulting in a significantly larger thrombus than in the absence of blood flow (17.1 +/- 2.1 vs 9.2 +/- 0.9 x 10(-2) mm2, p < 0.01). Stasis of the arterial blood per se did not affect the duration of thrombotic occlusion or increase plasma fibrinolytic activity. Thus, arterial occlusion caused by a thrombus arising at arterial bifurcations may be prolonged because of enlargement of the thrombus owing to the action of platelets in blood flowing through the intact branch.

Aminocaproic Acid↗
PubMed1997

Effect of different concentrations of amino acids in human serum and follicular fluid on the development of one-cell mouse embryos in vitro.

As a model for establishing an optimized medium for human in vitro fertilization (IVF), modified human tubal fluid (HTF) media containing amino acids at concentrations found in human serum and follicular fluid were prepared, and the effect of the media on development of random-bred (ICR) and F1 hybrid (CBF1) mice embryos was studied. The total concentrations of amino acids found in serum and follicular fluid were about one-third to one-half the concentrations present in two conventional media used in human IVF: Ham's F-10 and Eagle's minimal essential medium (MEM). When ICR mouse embryos were cultured in the HTF medium containing 21 amino acids at concentrations found in follicular fluid, the number of embryos developing to morulae at 72 h and to blastocysts at 96 h increased in comparison with those cultured in HTF medium. When HTF containing amino acids at concentrations found in serum was used, only induced morula formation at 72 h was enhanced. The number of hatching blastocysts at 96 h also increased when CBF1 mouse embryos were cultured with HTF supplemented with amino acids at concentrations found in follicular fluid. When ICR mouse embryos were cultured in modified HTF media containing concentrations of amino acids found in Ham's F-10 and MEM that contained higher concentrations of glutamine, embryo development was inhibited. The amount of ammonium produced during incubation for 3 days was significantly less when embryos were cultured in media containing concentrations of amino acids found in follicular fluid compared with when Ham's F-10 or MEM was the culture medium. Ammonium is produced by the breakdown of glutamine in the culture medium during incubation with or without embryos. These results suggest that the concentrations of amino acids found in follicular fluid are more effective and safer for embryo culture than those in other media currently in use.

Amino Acids↗
PubMed1997

Selective modification of somatosensory evoked potential during voluntary finger movement in humans.

We examined changes in somatosensory evoked potentials (SEPs) during voluntary movement of fingers innervated by the stimulated nerve and those not innervated by the stimulated nerve and the relationship to the kind of movement modality. Analysis showed that the amplitude of most components at F3, C3', and P3, except for P45 at C3, N35 and P45 at P3, decreased during voluntary finger movement tasks. Further, we found that the components of P40 at F3, P45 at C3', and N35 at P3 were increased during the voluntary pulling movement of the second and the third digits compared to those during the voluntary pushing movement of the fourth and the fifth digits, whereas all other components were decreased at F3, C3', and P3. We also found that not all components of SEPs were decreased while some SEPs in middle latency were increased. In conclusion, we confirmed the selectivity in attenuation of the SEPs. Moreover, we noted an interesting finding that the selectivity of attenuation of the SEPs was most frequently observed in the N20, P30 (P25 at F3), N35 (N30 at F3), and P45 (P40 at F3) components at F3, C3', and P3.

Adult↗
PubMed1997

Protective effect of nafamostat mesilate in early wound healing.

BACKGROUND: Tensile strength in rat ileal anastomosis is diminished after injection with superoxide dismutase. We have studied the immunohistochemistry of extracellular matrix to investigate changes associated with this loss of tensile strength. A serine proteinase inhibitor, Nafamostat mesilate, was used to evaluate its potential for maintaining tensile strength. STUDY DESIGN: Four groups of rats underwent ileal anastomosis, Groups 1 and 2 were controls. Groups 3 and 4 were given superoxide dismutase and Nafamostat mesilate, respectively, after anastomosis. RESULTS: In controls, groups 1 and 2, tensile strength decreased to 58 percent and 57 percent, respectively, of the initial value measured immediately after anastomosis 1 day postoperatively and both dropped to 33 percent 3 days postoperatively. After 5 days, tensile strength recovered to 83 percent of initial value. In comparison with controls, administration of superoxide dismutase significantly attenuated the loss of tensile strength on day 1 (94 percent of initial value, p < 0.01) and on days 3, 5 and 7 (p < 0.05). Similar results were found after administration of Nafamostat mesilate on days 3 and 5 (p < 0.05). In group 1, degradation of the collagen layer in the anastomosis was observed, with disappearance of immunostaining for fibronectin and vitronectin on day 3. In both groups 3 and 4, these changes were significantly attenuated with intense immunostaining for plasminogen activator inhibitor-1; fibronectin and vitronectin were seen particularly among collagen fibers on both sides of the anastomosis. CONCLUSIONS: These findings suggest that degradation of extracellular matrix causes loss of tensile strength early after anastomosis. Nafamostat mesilate may be clinically useful to prevent breakdown of intestinal anastomoses.

Anastomosis, Surgical↗
PubMed1997

Changes in central motor-sensory system following voluntary movement of stimulated finger.

OBJECTIVE: We examined which components of somatosensory evoked potentials (SEP) were modulated during the voluntary movement of stimulated fingers and discuss our findings with respect to the decrease in SEPs in terms of both centrifugal and centripetal mechanisms. METHODS: The study was performed in the Laboratory of Physiology, Institute of Health and Sport Sciences, University of Tsukuba. Experiments were performed on 10 healthy young male subjects, aged 19-21 years. All subjects were right-handed and were free of neurological disease. RESULTS: We found that N20-P25 (P22 at frontal area) -N35-(N30 at frontal) P45 (P40 at frontal area) components at the F3, the C3' and the P3 were consistently evoked, but N35 was increased at P3 and N30 attenuation at F3 during a sustained voluntary movement. Furthermore, the present experiments showed that frontal N30 was markedly decreased during a sustained voluntary movement. We also found that all SEPs components, except for parictal N35, were significantly decreased during sustained voluntary movement tasks. CONCLUSIONS: We concluded that the suppression of SEPs appeared to be due to the interaction of both centrifugal and centripatal mechanisms. Namely, in a particular type of movement task, more prenounced afferent mechanisms may contribute to the decrease in SEPs, while in the other types of tasks, more pronounced afferent activities may contribute to the decrease in SEPs.

Adult↗
PubMed1997

[Current status of low-dose CDDP. 5-FU therapy for solid malignant tumors--nationwide questionnaire survey].

A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.

Antineoplastic Combined Chemotherapy Protocols↗