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Biomedical subjects

N Yasuda

Publications and source records attributed to N Yasuda.

At least 37 records · Page 2Linked to original sources

2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A(2B) adenosine receptor.

A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The m-primary benzamide derivative 15f was the most potent compound (IC(50)=0.017 microM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity. The IC(50) values in rat hepatocyte glucose assay correlated well with the IC(50) values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2)=0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor.

Adenine↗

Effects of a one-hour educational program on medical students' attitudes to mental illness.

A new 1-h educational program was developed to change attitudes towards mental illness, and was conducted on 95 first-year medical students in order to investigate its effects on their attitudes towards mental illness, using a pre- and postquestionnaire study design. A similar study without the program was conducted on 94 first-year medical students as controls. After the program, more students replied that they would accept former patients on relatively close social distance items. Favorable attitudinal changes were observed in terms of 'psychiatric services', 'human rights of the mentally ill', 'patients' independence in social life', and 'cause and characteristics of mental illness'. In contrast, no significant change was observed in the control group. These results suggest that attitudes towards mental illness could be changed favorably by this program.

Adolescent↗

Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice.

We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.

Animals↗

Preparation and characterization of biodegradable or enteric-coated microspheres containing the protease inhibitor camostat.

We have produced biodegradable or enteric-coated microspheres containing camostat mesylate, a protease inhibitor, using a water-oil-water emulsion solvent evaporation method. The characteristics of the microspheres were determined. When polylactic acid, a biodegradable polymer, was used as a wall material, the optimized microsphere obtained showed a loading efficiency of almost 95% and had a mean diameter of 30 microm. This microsphere showed a sustained-release profile, with nearly 25% of drug being released at seven days in a dissolution test. When hypromellose acetate succinate (AS-HG type, with a high content of succinyl group) was used as an enteric wall material, optimized microspheres showed a loading efficiency of almost 80%. In this case, pH 3.0 citrate buffer was used as an internal aqueous phase, and citrate buffer containing 0.5% polyvinylalcohol was used as the external aqueous phase. These microspheres showed a rapid release profile in pH 6.8 buffer, whereas the release was extremely slow in pH 1.2 buffer. Hypromellose acetate succinate microspheres were also prepared containing 10% (w/w) N-benzoyl-dl-arg-4-nitroanilide as a model substrate for trypsin, with or without 5% (w/w) camostat. These microspheres were incubated in pH 6 or 7 buffer containing trypsin at 37 degrees C. When camostat was included in the microspheres, the substrate was protected from attack by trypsin, while in the absence of camostat, the released substrate was immediately attacked by trypsin to produce the degradation product N-benzoyl-dl-arginine.

Buffers↗

Preparation and characterization of insulin-loaded acrylic hydrogels containing absorption enhancers.

The objectives of this study were to prepare insulin-loaded acrylic hydrogel formulations containing various absorption enhancers, to perform in vitro and in vivo characterization of these formulations, and to evaluate the factors which affecting insulin availability on rectal delivery of insulin using this hydrogel system. The acrylic block copolymer of methacrylic acid and methacrylate, Eudispert, was used to make the hydrogel formulations. As absorption enhancers, 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD), lauric acid (C12), or the sodium salt of C12 (C12Na), were incorporated into the hydrogels. In an in vitro release test, the release rate of insulin from the hydrogels decreased as the polymer concentration of the hydrogel increased. The addition of C12Na to the hydrogel further increased the insulin release rate, which was greater at higher concentrations of the enhancer. A portion of the C12Na was found to remain bound to the acrylic polymer in dissolution medium. Serum insulin levels were determined at various time points after the administration of insulin solution or insulin-loaded (50 units/kg body weight) Eudispert hydrogels containing 5% (w/w) of C12, C12Na, or DM-beta-CyD to in situ loops in various regions of the rat intestine. The most effective enhancement of insulin release was observed with formulations containing C12Na. The bioavailability of insulin from the hydrogels was lower than that from the insulin solutions. Hydrogel formulations containing 7% or 10% Eudispert remained in the rectum for 5 h after rectal administration. However, the 5% (w/w) C12Na solution stained with Evan's-blue had diffused out and the dye had reached the upper intestinal tract within 2 h. Finally, the rectal administration of insulin-loaded hydrogels, containing 4%, 7%, or 10% (w/w) Eudispert and 5% (w/w) of enhancer (C12, C12Na, or DM-beta-CyD) to normal rats was shown to decrease serum glucose concentrations. The greatest effect was found with insulin-loaded 7% (Eudispert) hydrogel containing C12Na which having cosiderable large insulin release rate and bioadhesive characteristics.

Acrylates↗

Teratoma in a feline unilateral cryptorchid testis.

A 14- x 12- x 6-cm (approximately 600 g) cryptorchid testis was surgically removed with the omentum from the posterior portion of the abdominal cavity of a 2-year-old male American Shorthair cat. At the time of a previous orchiectomy, a unilateral testis had been discovered in the scrotum. The cut surface of the cryptorchid testis consisted of solid areas with many cysts containing fluid and spongy soft areas. Histologically, the cryptorchid testis was composed of neuroectodermal components and diffuse immature glial tissues, cystic, tubular, and papillary epithelial tissues, and immature cartilaginous tissues. A metastatic mass in the omentum had histologic structures similar to those of the cryptorchid testis. The present case was diagnosed as teratoma in a feline unilateral cryptorchid testis.

Animals↗

Reference values and limited serological survey for the Iriomote cat in Japan.

Clinical investigations and hematological, serum biochemical, and serological surveys were carried out on 11 male and 6 female Iriomote cats (Felis iriomotensis) in Japan. Examined Iriomote cats were considered clinically healthy by the inspection for the general physical conditions. However, urinalysis suggested the inflammation of the urinary tract in all the cats. Antibody for feline panleukopenia virus was positive in one of the examined Iriomote cats, which suggested a previous infection.

Animals↗

Multiple prolactin-releasing activity in the bovine hypothalamic extract.

The prolactin (PRL)-releasing activity (PRA) in the bovine hypothalamic extract (BHE) was compared to that of known substances with PRA and further characterized by gel filtration and reversed-phase high performance liquid chromatography (RP-HPLC). Crude BHE produced marked dose-dependent stimulation of PRL secretion from the cultured rat adenohypophysial cells. Among the synthetic substances examined, vasoactive intestinal peptide (VIP), thyrotropin-releasing hormone (TRH) and beta-endorphin (END) showed significant PRA. However, the flatter dose-response slope for TRH compared with BHE or the small amounts of VIP and END in BHE suggested that these peptides could not account for the major active elements of BHE. Oxytocin and interleukin-1beta were also tested, but they exhibited no PRA in our assay system. Gel filtration of BHE on the Sephadex G-100 column yielded two peaks of PRA distinct from TRH, VIP and END. One eluted in the void and the other in more retarded fractions. The latter fractions were pooled and subjected to the two-step RP-HPLC. The PRA was separated into three peaks designated peaks I, II and III in the first RP-HPLC experiment. Furthermore, the second RP-HPLCs with finer resolution revealed that peak II as well as peak III consisted of three peaks, while peak I eluted as a single peak. Most of these seven PRA peaks exhibited different RP-HPLC profiles from those of the newly characterized PRL-releasing peptides. These findings again provide confirmatory evidence that BHE contained unique factors different from the above known substances.

Animals↗

4-Vinylbenzoic acid and 9-vinylanthracene.

The crystal structures of two styrene analogues, 4-vinylbenzoic acid, C(9)H(8)O(2), (I), and 9-vinylanthracene, C(16)H(12), (II), were determined by X-ray analyses at 108 and 293 K for (I) and at 123 and 293 K for (II). In (I), a pair of molecules around an inversion center form a dimer connected by two carboxyl groups. The anthracene planes of two molecules in (II) are antiparallel to each other around an inversion center. The vinyl group of (I) is almost coplanar with the phenyl ring, whereas the vinyl group of (II) is nearly perpendicular to the anthracene plane. In (I), the bond length of the vinyl group at 293 K is significantly shorter than that at 108 K [1.288 (2) versus 1.3248 (14) A] suggesting a bias of the thermal motion, whereas the bond lengths are not so different between the two temperatures in (II) [1.3266 (15) versus 1.310 (2) A].

Journal Article↗

Polychlorinated dibenzo-p-dioxin and dibenzofuran concentrations in the serum samples of workers at continuously burning municipal waste incinerators in Japan.

OBJECTIVES: To find whether concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in serum increased in workers at municipal incinerators that burn continuously. METHODS: 30 Workers employed at three municipal waste incineration plants (incinerator workers) and 30 control workers were studied. The incinerator workers had worn dust masks or airline masks during the periodic repair work inside the incinerators. Previous job, dietary habit, smoking habit, distance from residence to the incineration plant, and body weight and height were obtained from a questionnaire survey. Concentrations of PCDDs/PCDFs were measured in the serum of the workers and the dust deposited in the plants. The influence of various factors on serum concentrations of PCDDs/PCDFs was examined by multiple regression analysis. RESULTS: Dust analysis showed the greatest amount of octachlorodibenzo-p-dioxin (OCDD), followed by 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), 1,2,3,4,6,7,8-heptachlorodibenzofuran (HpCDF), and octachlorodibenzofuran (OCDF). The toxicity equivalents (TEQs) of PCDDs and PCDFs in the deposited dust were 4.8, 1.0, and 6.4 ng TEQs/g, respectively, for plants A, B, and C. The mean serum TEQs of PCDDs and PCDFs in the incinerator workers and control workers were 19.2 and 22.9 pg TEQs/g lipid, respectively, for area A, 28.8 and 24.5 pg TEQs/g lipid for area B, and 23.4 and 23.6 pg TEQs/g lipid for area C. No significant differences were found between the incinerator workers and the controls for TEQs of PCDDs and PCDFs separately, and TEQs of PCDDs and PCDFs together. However, the serum 1,2,3,4,6,7,8-HpCDF concentration was significantly higher in the incinerator workers than in the controls for all the three areas. When the exposure index to 1,2,3,4,6,7,8-HpCDF is defined as the product of the concentration of 1,2,3,4,6,7,8-HpCDF in the deposited dust and duration of employment, the concentration of 1,2,3,4,6,7,8-HpCDF in serum increased as the exposure index increased. Multivariate analysis suggested that the serum concentration of HpCDF increased with duration of employment at the incineration plants and OCDF increased with employment of > or = 21 years. The other significant variables (p < 0.01 or p < 0.001) were area for hexachlorodibenzo-p-dioxin (HxCDD) and tetrachlorodibenzofuran (TCDF), Brinkman index for HpCDD, and body mass index (BMI) for tetrachlorodibenzo-p-dioxin (TCDD), HpCDD, and TEQs of PCDDs. CONCLUSION: The serum TEQs of PCDDs and PCDFs was not significantly higher among the incinerator workers, but the serum concentration of 1,2,3,4,6,7,8-HpCDF was. This suggests that the incinerator workers had inhaled dust containing PCDDs and PCDFs while working in plants equipped with incinerators that burn continuously.

Adult↗

[Analyses of work-relatedness of health problems among truck drivers by questionnaire survey].

In order to estimate occupational risk factors for health problems among truck drivers, a questionnaire survey of working conditions, job content in truck transportation, subjective symptoms and present illnesses was carried out among 541 truck transportation workers in 1997. The valid response rate was 85.7%, and 134 local truck drivers, 199 long-distance truck drivers and 71 clerical workers were analyzed. First, to examine occupational risk factors and health problems among the three groups, the authors analyzed working conditions, job content in truck transportation, subjective symptoms and present illnesses. Second, to estimate the work-relatedness of health problems among local truck drivers and long-distance truck drivers, logistic regression analyses were conducted, and odds ratios and 95% confidence intervals were computed. The prevalence rates of working factors affecting health problems of truck drivers were significantly higher than those of clerical workers in the items on irregular shift work, working environment, working posture, handling heavy materials, job stress due to overloading and long working time and limited time off. The prevalence rates for subjective symptoms (ringing in the ears, neck pain and low back pain) and present illnesses (hypertension, ulcers in the digestive tract, back injuries, whiplash injuries and hemorrhoids) among truck drivers were significantly higher than those of clerical workers. In logistic regression analyses, many work-related items except age, BMI and smoking habit showed significantly higher odds ratios for subjective symptoms and present illnesses of truck drivers. Odds ratios for hypertension, heart diseases and related subjective symptoms among local truck drivers were significantly increased by job career, twisting posture, vibration and driving stress. Odds ratios for gastro-duodenal diseases and related subjective symptoms were significantly increased by narrow working space, sleeping in the truck, driving distance, squatting posture and driving stress. Odds ratios for ringing in the ears among local truck drivers were significantly increased by job career, long working time, narrow working space, sleeping in the truck and driving stress. Odds ratios for musculo-skeletal diseases and related subjective symptoms were significantly increased by overwork, vibration, narrow working space, sitting posture and shortage of recess. Odds ratios for fatigue symptoms were significantly increased by the shortage of recess, vibration and driving stress. In order to cope with the health problems of truck drivers, it is recommended that working conditions and work loads for among truck drivers as described above be improved.

Automobile Driving↗

Effects of medical education on attitudes towards mental illness among medical students: a five-year follow-up study.

In order to clarify the effects of medical education on attitudes towards mental illness among medical students, a follow-up study was conducted. All 100 students entering Kochi Medical School in 1988 were subjects. The initial questionnaire survey was conducted in 1988, and followed up in 1993. Response rate was 69% in the initial survey, and 83% in the follow-up study. By the time of the follow-up, all of the students had completed their medical education, including courses in psychiatry and mental health. Results were as follows: At the follow-up study, 1) a significantly higher percentage of students replied that they accepted the mentally ill as co-workers; 2) significantly favorable changes were observed in attitudes towards psychiatric services; 3) optimism about the effectiveness of treatment for mental illness at an early stage and prevention of mental illness had decreased; and 4) no change was observed in attitudes toward human rights of the mentally ill, except in the case of one item stating that the mentally ill should not have children in order to avoid hereditary handicaps, with which a lower percentage agreed. Conclusively, medical education can play an important role in attitudes towards mental illness.

Attitude of Health Personnel↗

Effects on mortality of getting the basic health examination under the Health Services for the Elderly Act and modification of the effects by health status among elderly persons in a rural community.

This longitudinal study examines the effect on mortality of regular use of the basic health examination under the Health Services for the Elderly Act and heterogeneity of the effect according to levels of physical and mental health status among community dwelling elderly persons. Of persons aged 65 and older who lived in Otsuki town, Kochi prefecture, and completed a questionnaire survey about health in February 1991, 1,470 survivors on the anniversary of the baseline survey were followed by the end of March 1996. Regularity of getting the examination was determined by the history of use of the examination in 1990 and 1991. Mortality reduction associated with annual use of the examination was observed in both the 65-74 and the 75 and older age groups and the benefit got smaller with advancing in age. In the 75 and older age group, the benefit from annual use of the examination was restricted to persons having no impairment in physical activities of daily living and those having favorable mental health. Biennial use of the examination was associated with the same amount of mortality reduction as annual use among persons having chronic conditions under treatment in the 65-74 age group. Regular use of the basic health examination at old ages is effective and the effectiveness varies by age range and level of functional health status.

Aged↗

[Occupational health services to assist workers' health promotion based on a participatory training program of staff members for public health centers].

Work-related health problems among employees of small-scale enterprises and un-employed workers are still serious in Japan. Occupational health services related to their working conditions and environment are limited and more provison needs to be made. Our participatory training program is aimed at allowing staff members of public health centers to provide occupational health services and assist workers' health promotion. In this program, participants examine occupational risk factors affecting workers' health problems with ergonomic check-lists and discuss potential improvements in the workplace. Participants experience practical visits to small-scale enterprises in their communities and the resultant occupational health services are discussed and evaluated at the final step in this program. The essential feature of successful case was that the public health center had coordinated community resources and occupational health services with ergonomic check-lists accepted by small-scale enterprises. This participatory training program is effective from the viewpoint of evaluating occupational risk factors affecting workers' health problems and proposing improvements in the workplace. In order to optimally provide occupational health services for the employees of small-scale enterprises and un-employed workers, the community resources including health facilities and the parties concerned must be organized and utilized effectively.

Education↗

[The investigation of the testing method on fracture toughness of dental adhesive resins].

OBJECTIVE: The testing method for mode I fracture toughness (GIC) of dental adhesive resins was investigated. METHODS: The dental adhesive resins were placed between two Co-Cr alloy plates to make up test specimen, so test specimen had a metal/adhesive resin/metal construction. The category of adhesive resins, the dimensions of test specimen and testing speed were used as the variants. The testing method for mode I fracture toughness (GIC) was investigated by using double cantilever beam (DCB) testing. The correlation between the GIC and each factor was analysed by regression analysis. RESULTS: In all test specimens, it was found that the values of fracture toughness (GIC, GIR) at the process of crack propagation were nearly constant. Therefore, it was found that fracture toughness (GIC) at maximal load might only be measured to evaluate an adhesive resin. On the values of GIC, there was no effect from the dimensions of the test specimens, width (b = 3.5 mm), thickness (2 hm = 2.4 mm), initial crack length (ao = 10-19 mm) and testing speed(Vc = 0.1 mm/min, 0.2 mm/min). But, it was found that the fracture toughness was influenced by thickness of adhesive layer (hr). In case of SB, the value of GIC had a tendency to increase as the adhesive layer became thicker, and then the crack propagating area observed as cohesive failure became remarkably rougher. In case of PV, the values for hr = 100 and 200 microns were similar, however, that for hr = 20 microns somewhat decreased resulting in an interfacial failure. By the way, cohesive failures of hr = 100 and 200 microns were observed as similar flat surfaces. CONCLUSION: Fracture toughness was not influenced very much by the dimensions of test specimen, but was influenced by thickness of adhesive layer. Thus, it was recognized that this testing method was more effective for evaluating the adhesive resin.

Materials Testing↗

Schizophrenia and the influenza epidemics of 1957 in Japan.

BACKGROUND: We tested the hypothesis that the exposure to an influenza epidemic during the second trimester of gestation is associated with an increased risk of later development of schizophrenia. METHODS: There were three influenza epidemics (A/B mixed type, the first A2 type and the second A2 type) in 1957 in Kochi, Japan. We compared the risk of developing schizophrenia in birth cohorts exposed to these three influenza epidemics during gestation with that in birth cohorts not exposed. To identify subjects who had developed schizophrenia, we surveyed patients with schizophrenia who received medical care at all psychiatric institutions in Kochi prefecture. RESULTS: There is a pattern that schizophrenic births increase twice or more among female subjects who were exposed to each of three influenza epidemics in the fifth month of gestation. The increase in the female births exposed to the second A2 epidemic was significant (relative risk 2.86, 95% confidence interval 1.37-5.26). This pattern across the three epidemics was not observed in male subjects. CONCLUSIONS: Prenatal exposure to an influenza epidemic during the second trimester increased the risk of later development of schizophrenia in female births.

Child↗