Massage therapy for home care patients using the health insurance system in Japan.

OBJECTIVES: To clarify the status of home care massage services provided to patients. This will help in understanding how many patients utilize this service and the circumstances under which treatment is provided. DESIGN: A retrospective study. SETTING: Fifty-four acupuncture, moxibustion, and massage clinics. Participants were patients who had received home care massage for six months or more. We collected a total of 1587 responses from these 54 massage clinics; of these, 1415 responses (mean age = 79.1 ±â€¯11.5 years) were valid (valid response rate 89.2%). MAIN OUTCOME MEASURES: Actual patients and actual care services. RESULTS: The most common disorder observed among patients who utilized home care massage services was cerebrovascular disease (at approximately 36%), while the second most common were arthropathy-related disorders (16.3%). Although most patients received massage, approximately 30% received manual therapy (e.g. manual correction) and hot fomentation as part of thermotherapy. Notably, only around 10% of patients received massage alone; the majority received treatment in combination with range of motion and muscle-strengthening exercises. CONCLUSIONS: This study helped to clarify the actual state of patients receiving home care massage and the details of the massage services provided. This study clearly showed the treatment effectiveness of massage, which can be used by home medical care stakeholders to develop more effective interventions.

Analysis of morphological changes after facial massage by a novel approach using three-dimensional computed tomography.

BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation of facial morphological changes. Here, we describe a three-dimensional computed tomography (3D-CT) method for objective analysis of facial and intra-facial (subcutaneous) changes. The effects of facial massage were examined using both methods. METHODS: Subjects were 12 healthy female volunteers without facial scars or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of massage-induced morphological changes was done at the nasolabial folds, upper, lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA-skin surface distances (VSDs) were measured. Massage-induced changes of VSD were calculated (facial massage-induced change rate, FMCR). Intra-facial (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring revealed marked morphological changes of the nasolabial folds after facial massage, and changes of the lower, upper and lateral cheeks and lower eyelid were also observed in more than half of the subjects. FMCR values were significantly changed in the paranasal area, nasolabial fold area and cranial part of the mandibular area. Photograph-based scores at the lower cheek and lower eyelid were well correlated with FMCR in the inferior part of the nasolabial fold and the mandibular area, respectively. Massage-induced changes of subcutaneous fat tissues and facial expression muscles were also apparent on CT images. CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of facial massage, including anatomical changes in subcutaneous structures.

Evaluation of combined docetaxel and nedaplatin chemotherapy for recurrent esophageal cancer compared with conventional chemotherapy using cisplatin and 5-fluorouracil: a retrospective study.

This retrospective study evaluated the safety and efficacy of combination chemotherapy using docetaxel and nedaplatin in an outpatient setting compared with those of chemotherapy using cisplatin (CDDP) and 5-Fu under hospitalization. Subjects comprised 21 patients who had been diagnosed with recurrent esophageal squamous cell carcinoma (ESCC), with 10 patients receiving combination chemotherapy comprising CDDP and 5-fluorouracil (5-Fu) under hospitalization (FP group; n = 10), and 11 patients receiving combination chemotherapy comprising docetaxel and nedaplatin in an outpatient setting (Doc/Ned group; n = 11). In the Doc/Ned group, patients received 30 mg/m(2) of docetaxel over a 1-h infusion on day 1, followed by 40 mg/m(2) of nedaplatin over a 2-h infusion on day 1 in an outpatient setting. In the Doc/Ned group, complete response was observed in two patients (18.1%), one with liver metastasis and one with abdominal lymph node metastasis, and two (18.1%) achieved partial response. In contrast, no complete responses were obtained in the FP group, and partial response was observed in only one patient (10.0%) with local recurrence. Response rates were thus 36.3% for the Doc/Ned group and 10.0% for the FP group. With a median follow-up of 234 days in the Doc/Ned group and 279 days in the FP group, median survival time (MST) was 234 days in the Doc/Ned group and 378 days in the FP group. No significant differences in MST were identified between groups. Thus regimen based on docetaxel and nedaplatin allows administration on an outpatient basis and appears feasible for recurrent ESCC as a second-line chemotherapy.

Hochu-ekki-to inhibits rhinovirus infection in human tracheal epithelial cells.

BACKGROUND AND PURPOSE: A traditional Japanese herbal medicine, hochu-ekki-to, has been used for the symptomatic treatment of the common cold and to reduce the frequency of colds in patients with chronic obstructive pulmonary disease. However, the inhibitory effects of hochu-ekki-to on infection by rhinovirus (RV), the major cause of common colds, have not been studied. EXPERIMENTAL APPROACH: Human tracheal epithelial cells in culture were infected with a major group rhinovirus-RV14. Virus output and viral RNA were measured along with interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha), mRNA for intercellular adhesion molecule (ICAM)-1 and acidic endosomes in cells. KEY RESULTS: RV14 infection increased virus titers, the content of cytokines in supernatants and RV14 RNA in the cells. Hochu-ekki-to decreased virus output, RV14 RNA in the cells, susceptibility to RV infection and supernatant cytokine concentrations after RV14 infection. Hochu-ekki-to reduced mRNA for ICAM-1, the receptor for RV14, the concentration of the soluble form of ICAM-1 and the number and fluorescence intensity of acidic endosomes in the cells, from which RV RNA enters into the cytoplasm, at RV14 infection. Glycyrrhizin, one of the chemical constituents of hochu-ekki-to, reduced supernatant virus titers dose-dependently. CONCLUSION AND IMPLICATIONS: Hochu-ekki-to inhibited RV14 infection by decreasing ICAM-1 and by blocking entry of viral RNA into the cytoplasm from the endosomes, in airway epithelial cells. Glycyrrhizin may be partly responsible for inhibition of RV infection by hochu-ekki-to. Hochu-ekki-to could modulate airway inflammation by reducing production of cytokines in RV infections.

Isolation and characterization of a human thiamine pyrophosphokinase cDNA.

A human thiamine pyrophosphokinase cDNA clone (hTPK1) was isolated and sequenced. When the intact hTPK1 open reading frame was expressed as a histidine-tag fusion protein in Escherichia coli, marked enzyme activity was detected in the bacterial cells. The hTPK1 mRNA was widely expressed in various human tissues at a very low level, and the mRNA content in cultured fibroblasts was unaffected by the thiamine concentration of the medium. The chromosome localization of the hTPK1 gene was assigned to 7q34.

Dichotomous effect of a traditional Japanese medicine, bu-zhong-yi-qi-tang on allergic asthma in mice.

To determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT), for the control of allergic disease, we examined the effects of oral administration of HOT on a murine model of asthma allergic responses. When oral administration of HOT was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. The serum levels of OVA-specific immunoglobulin (Ig)E and IgG1 were significantly decreased, whereas the level of OVA-specific IgG2a was increased. Interleukin (IL)-4 production by spleen T cells in response to OVA was significantly suppressed, while Interferon (IFN)-gamma production was increased in mice treated with HOT in the induction phase. On the other hand, HOT given in the eliciting phase induced a predominant Th2 response with increased IgE production in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of HOT dichotomously modulates allergic inflammation in a murine model for asthma, thus offering a different approach for the treatment of allergic disorders.

Thermochemical transformation of sulfur compounds in Japanese domestic Allium, Allium victorialis L.

Sulfur compounds contributed to the health promotion in Allium species are produced via enzymic and thermal reactions. Potent antithrombotic agents which have been identified as allyl trisulfides, dithiins, and ajoene in garlic (A. sativum) and caucas (A. victorialis) are thermochemically transformed from allicin (allyl 2-propenethiosulfinate). The leaves and stems of Japanese domestic Allium plant, A. victorialis L. which is widely distributed in the northern part of Japan, under the name "Gyoja-ninniku" is a nutritious vegetable. The significant flavor compounds of caucas are methyl allyl disulfide (Chinese chive odor), diallyl disulfide (garlic-like odor), and dimethyl disulfide and methyl allyl trisulfide (pickles-like odor) among more than 85 peaks on the gas chromatogram. 2-Vinyl-4H-1,3-dithiin and 3,4-dihydro-3-vinyl-1,2-dithiin as platelet aggregation inhibitors were found eliminated in dichloromethane extract of caucas. The significant health promoting factors, allyl trisulfides and dithiins were relatively increased when caucas was cooked on a frying pan.

Molecular cloning and expression of a mouse thiamin pyrophosphokinase cDNA.

Thiamin pyrophosphokinase (EC 2.7.6.2) catalyzes the pyrophosphorylation of thiamin with adenosine 5'-triphosphate to form thiamin pyrophosphate. A mouse thiamin pyrophosphokinase cDNA clone (mTPK1) was isolated using a combination of mouse expressed sequence tag database analysis, a two-step polymerase chain reaction procedure, and functional complementation screening with a Saccharomyces cerevisiae thiamin pyrophosphokinase-deficient mutant (thi80). The predicted protein contained 243 amino acid residues with a calculated molecular weight of 27,068. When the intact mTPK1 open reading frame was expressed as a glutathione S-transferase fusion protein in Escherichia coli lacking thiamin pyrophosphokinase, marked enzyme activity was detected in the bacterial cells. The corresponding 2.5-kilobase pair mRNA was expressed in a tissue-dependent manner and was found at relatively high levels in the kidney and liver, indicating that the mode of expression of mTPK1 genes differs with cell type. The expression of mTPK1 genes in cultured mouse neuroblastoma and normal liver cells was unaffected by the thiamin concentration in the medium (10 microM versus 3.0 nM). This is the first report on identification of the primary sequence for mammalian thiamin pyrophosphokinase.

Control of vascular smooth muscle cell growth in fowl.

In adult domestic fowl, angiotensin (ANG) receptors are present in the vascular smooth muscles (VSM) and in the endothelium, mediating vasorelaxation via endothelium-derived relaxing factor/cGMP. ANG II-induced relaxation is minor in chicks and becomes more marked as they mature but diminishes in adult birds, whereas ANG II neither relaxes nor contracts endothelium-denuded aortae from mature chickens. The present study examines in cultured fowl aortic SM cells whether (1) ANG II stimulates or inhibits VSM cell growth and, if so, whether this growth-stimulatory or -inhibitory effect changes with maturation/aging, and (2) S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, and cGMP attenuate the basal or stimulated VSM cell growth. [Asp1, Val5]ANG II (native fowl ANG II, 10(-6) M) markedly increased (increase from vehicle control, 226.5%; P < 0.01) [3H]thymidine (Thd) incorporation into DNA of quiescent VSM cells (first subculture) from 6-week-old chicks. This growth-stimulating effect was reduced with age (41.4, 29.6, and 3.2% at 9, 19, and 43 weeks of age, respectively). In contrast, platelet-derived growth factor (PDGF, 20 ng/ml) increased [3H]Thd incorporation similarly in chicks, pullets, and hens. Furthermore, ANG II significantly (45.9%, P < 0.01) attenuated the growth-promoting effect of fetal calf serum in cultured VSM cells from 6-week-old chicks. This inhibitory effect also decreased in older birds. ANG II showed neither a growth-stimulatory nor -inhibitory effect in cultured neointimal cells. SNAP attenuated dose dependently (20-60 microM) the basal and PDGF-induced VSM cell growth, whereas cGMP inhibited basal growth only at a high dose (100 microM). These results indicate that in fowl VSM cells, ANG II is mitogenic and antimitogenic in chicks but not in mature birds, suggesting that phenotypic modulation occurs in the ANG receptors/signaling mechanism with maturation/age or in neointimal cells, whereas the mitogenic mechanism via PDGF remains in both young and mature birds.

Synthesis and pharmacological activity of triazolo[1,5-a]triazine derivatives inhibiting eosinophilia.

In continuation of our previous work on eosinophilia inhibitors, we synthesized an additional series of inhibitors, which consisted of 5-amino-1-[(methylamino)thiocarbonyl]-1H-1,2,4-triazole derivatives and a newly developed series of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives. We evaluated their inhibitory activity on the airway eosinophilia model, which was induced by the intravenous (iv) injection of Sephadex particles. In the 1,2,4-triazole series with various substituents at the 3 position of the triazole ring such as 2-furyl, pyridyl, and phenoxy, none of derivatives had comparable activity to the previously reported compound GCC-AP0341, 5-amino-3-(4-chlorophenyl)-1-[(methylamino)thiocarbonyl]-1H-1,2, 4-triazole. In the triazolo[1,5-a]triazine series, 2-(4-chlorophenyl)-6-methyl-1,2,4-triazolo[1,5-a]-1,3, 5-triazine-7(6H)-thione (3h) was highly potent, and when given orally it had an ID50 value of 0.3 mg/kg, which is comparable to that of GCC-AP0341. The fact that the structure-activity relationship of these two series was quite similar suggests that a common substructure, such as the 1,2,4-triazole ring with a substituted phenyl ring at the 3 position and a thiocarbonyl moiety at the 1 position, could contribute to the activity. Our selected compound 3h was less active than GCC-AP0341 in the antigen-induced hyper-responsiveness model in guinea pigs; however, we plan to carry out further studies on eosinophil functions, especially on their activation, using our two compounds, 3h and GCC-AP0341.

[Sairei-to inhibits the production of endothelin-1 by nephritic glomeruli(2): alisols, possible candidates as active compounds].

We have previously reported that Sairei-to (TJ-114), a Japanese herbal medicine, prevented the production of endothelin-1 in anti-GBM nephritic rats, and that Alismatis Rhizoma (Takusha in Japanese), one of the twelve herbs composing TJ-114, might be responsible for the action. In order to further clarify the antinephritic components of TJ-114, we investigated the effects of Takusha extracts on various parameters, including endothelin-1 production of glomeruli in vitro and in vivo using anti-GBM nephritic rats. MeOH-100% MeOH and MeOH-50% MeOH fractions (31.3 microgram/ml or higher) strongly inhibited an increase in endothelin-1 concentration in culture medium when they were added to a culture of glomerular cells derived from nephritic rats. In addition, oral administration of the MeOH-100% MeOH fraction (30 mg/kg) ameliorated the proteinuria, increase in systolic blood pressure and changes in histopathological parameters in nephritic rats. Oral administration of the MeOH-100% MeOH fraction inhibited increase in endothelin-1 expression in the glomeruli of nephritic rats and in endothelin-1 production by a culture of glomerular cells derived from the nephritic rats. Alisols A and B, the main constituents of the MeOH-100% MeOH fraction, inhibited in vitro endothelin-1 production by glomerular cells derived from the nephritic rats. Oral administration of alisol B (30 mg/kg) prevented the endothelin-1 expression by glomeruli and the increase in endothelin-1 production by cultured nephritic glomerular cells. Oral administration of alisol B also ameliorated the proteinuria, the increase in systolic blood pressure and the changes in histopathological parameters in the nephritic rats. These results indicate that the antinephritic action of TJ-114, resulting from the inhibition of endothelin-1 production, may be attributed to the alisols in Takusha.

Inhibition of DNA topoisomerases by microbial inhibitors.

New inhibitors of DNA topoisomerase named 2280-DTI and 2890-DTI have been discovered in the culture filtrates of Micromonospora sp. strain No. 2280 and Streptomyces sp. strain No. 2890, respectively. Both inhibitors were purified from each culture filtrate by column chromatography on Diaion, Dowex and gel filtration. Both inhibitors were thermostable acidic substances with high molecular weight and inhibited topoisomerase I in a non-competitive manner. They differed from well-known inhibitors of topoisomerases such as camptothecin and doxorubicin, which inhibit the DNA rejoining reaction of the enzyme by intercalation into DNA strands or stabilizing the cleavable complex (enzyme-DNA reaction intermediate). 2280-DTI and 2890-DTI did not intercalate into DNA strands and also had no ability to stabilize the cleavable complex. It is suggested that 2280-DTI and 2890-DTI inhibit the DNA breaking and rejoining reactions of topoisomerase by direct action on the enzyme molecule.

Anti-inflammatory activity of superoxide dismutase conjugated with sodium hyaluronate.

Superoxide dismutase (SOD) from bovine erythrocytes was conjugated with sodium hyaluronate (HA) with a mean molecular weight of 10(6) to have greater anti-inflammatory activity in vivo. Amino groups of SOD were coupled with carboxyl groups in the hyaluronate molecule using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The HA-SOD conjugate was composed of 1.5 mol of SOD molecule per 1 mol of hyaluronate on the average, and retained 70% of the activity of unmodified SOD. The conjugate was essentially non-immunogenic in mice, and exhibited much higher anti-inflammatory activities than HA or SOD in models of inflammatory diseases such as ischemic oedema of the foot-pad in mice, carrageenin-induced pleurisy and adjuvant arthritis in rats.

Structure of the mutant fibrillin-1 gene in the tight skin (TSK) mouse.

Mice carrying the tight skin (TSK) mutation harbors a 3.0-kb genomic duplication (exons 17-40) of the fibrillin-1 gene (Fbn-1) located on band F of chromosome 2 as TSK mutation. We cloned and sequenced the mutated Fbn-1 gene, since it is believed to be responsible for TSK syndrome. Sequence analysis showed numerous amino acid differences in the 5' and 3' segments between the TSK mutation and wild-type fbn-1 gene, but any amino acid difference between the TSK mutation and C57BL/6 mice. (TSK and C57B1/6 mice are genetically similar, differing only by TSK mutation.) Four amino acid differences were observed between two copies of TSK's fbn-1 gene encoded by exons 17-40. Our results suggest that the majority of structural differences occurred in the N and C termini segments during strain divergence and only a few after the duplication event.

Ultrastructural changes during myocardial hypertrophy and its regression: long-term effects of nifedipine in adult spontaneously hypertensive rats.

Nifedipine (20 mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N, n = 8). Comparison was done with sex-matched 15-week-old SHR (SHR-15, n = 7), untreated 35-week-old SHR (SHR-C, n = 10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15, n = 15), and 35-week-old WKY (WKY-15, n = 5). Light and electron microscopic data on the subepicardial, middle and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199 +/- 11 mmHg vs 121 +/- 13 mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.

Ovarian tumor complicated by a colo-ovarian fistula.

Although a fistula is a rare complication of ovarian tumor, we encountered four patients with cole-ovarian fistulas in three years. The first case was demonstrated by following barium enema by the extravasation of barium from the sigmoid colon, and by a gas-containing lesion in the tumor observed on computed tomography. Mature cystic teratoma was the pathological diagnosis in two cases. A mixed germ cell tumor and a serous cystadenoma of low malignant potential were diagnosed in the other two cases. The etiology and differential diagnosis of cole-ovarian fistula are reviewed.

Mutation thi81 causing a deficiency in the signal transduction of thiamine pyrophosphate in Saccharomyces cerevisiae.

We isolated a strain carrying a recessive constitutive mutation (thi81) for the expression of thiamine metabolism in Saccharomyces cerevisiae. The thi81 mutant exhibits significant thiamine transport, thiamine-repressible acid phosphatase (T-rAPase) activities and significant activities of enzymes involved in thiamine biosynthesis which are repressed in the wild-type strain in medium supplemented with thiamine (2 x 10(-7) M). The thi81 mutant exhibited the same level of thiamine pyrophosphokinase activity and intracellular thiamine pyrophosphate concentration as the wild-type strain in medium supplemented with exogenous thiamine. The mutant strain constitutively produced PHO3 mRNA encoding T-rAPase in medium supplemented with thiamine. These results suggest that the thi81 mutant lacks a negative factor involved in the regulation of the genes encoding proteins involved in yeast thiamine metabolism.

Effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates.

Inhibitory effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates were studied. The rhubarb solution inhibited both the amorphous calcium phosphate (ACP) formation and the rate of hydroxyapatite (HAP) transformation, and extended the induction time. When the solution was fractionated using membrane filters, a filtrate with the molecular weight between 3 and 10 kDa (with 2/3 recovery of polyphenols) was found to be responsible for both the ACP formation and the extension of the induction time. Another filtrate with the molecular weight below 3 kDa (with 1/3 recovery of polyphenols) may be responsible for the inhibition of both the ACP formation and the rate of HAP transformation, and the extension of the induction time. When the extract of rhubarb was fractionated using a Sephadex LH-20 column chromatography, fraction IV greatly inhibited the formation of calcium phosphate precipitates, while fractions I, II and III slightly inhibited that reaction. Our finding suggests that fraction IV may contain useful substance(s) for the prevention of oral calcium phosphate precipitation (calculus formation). However, strong calcium chelating properties would limit the concentration that could be safely employed.

Inhibition of mucosal lipid hyperoxidation by green tea extract in 1,2-dimethylhydrazine-induced rat colonic carcinogenesis.

Phosphatidylcholine hydroperoxide (PCOOH) measured using a chemiluminescence detector to examine colonic mucosal lipid hyperoxidation increased after injection of 1,2-dimethylhydrazine and green tea extract (GTE), which we previously showed inhibited carcinogenesis and oxidative DNA damage in the gastrointestinal tract. Therefore, the hyperoxidation of membrane phospholipids reflected well the degree of DNA damage and carcinogenic alteration, and may be a useful intermediate biomarker for initiation of carcinogenesis.

In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis.

BACKGROUND AND PURPOSE: Antiplatelet agents are widely used for the prevention of ischemic stroke. However, their effects on thrombus formation have rarely been evaluated in experimental animals in vivo. We introduce methods for evaluating antithrombotic action in gerbils and the effects of several antiplatelet agents on thrombus formation. METHODS: In gerbils 8 to 10 weeks of age, we tightly compressed the unilateral common carotid artery for 2 minutes using the device prepared for this purpose to damage the endothelium. Thrombus formation in the damaged artery was observed directly through the microscope for 30 minutes. In six animals, the damaged artery was examined immediately after the experiments by electron microscopy. We studied the effects of antiplatelets by injecting the drugs intravenously 10 minutes before endothelial damage. RESULTS: In control studies, 70% to 90% of animals developed thrombi after arterial compression. The electron microscopic examination displayed endothelial damage in association with platelet thrombus at the damaged site. Administration of 2 mg/kg aspirin, 3 and 10 mg/kg ticlopidine, and 0.3 and 1.0 mg/kg ibudilast, a novel prostacyclin accelerator, decreased the frequency of thrombus formation significantly, whereas 20 mg/kg aspirin and 20 mg/kg dipyridamole failed to decrease thrombus formation. CONCLUSIONS: This model is considered useful for evaluating the antithrombotic effects of drugs because of its feasibility and high reproducibility. The present results support the view that a lower dose of aspirin may prevent cerebral vascular accidents as efficiently as a higher dose of aspirin.