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Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 55 records · Page 3Linked to original sources

Control of medicine release from solid dispersion composed of the poly(ethylene oxide)-carboxyvinylpolymer interpolymer complex by varying molecular weight of poly(ethylene oxide).

Solid dispersion composed of the poly(ethylene oxide) (PEO)-carboxyvinylpolymer (CP) interpolymer complex containing phenacetin (PHE) was prepared by using nine grades of PEO having different molecular weights from 2000 to 4500000. We attempted to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO. The physicochemical properties of the solid dispersion were analyzed by powder X-ray diffractometry and thermal analysis. The interaction between PEO and CP was analyzed by IR spectroscopy. Transmittance of the polymer solution was measured to study the complexation between PEO and CP. The release profile of PHE varied depending on the molecular weight of PEO. The minimum release rate was observed at the PEO molecular weight of 35000. It was found that the amount of the PEO-CP complex formation by hydrogen bonding changed depending on the molecular weight of PEO. These results indicate that it is feasible to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO.

Analgesics, Non-Narcotic↗

Suppression of agglomeration in fluidized bed coating. II. Measurement of mist size in a fluidized bed chamber and effect of sodium chloride addition on mist size.

It has been reported that the degree of particle agglomeration in fluidized bed coating is greatly affected by the spray mist size of coating solution. However, the mist size has generally been measured in open air, and few reports have described the measurement of the mist size in a chamber of the fluidized bed, in which actual coating is carried out. Therefore, using hydroxypropylmethyl cellulose (HPMC) aqueous solution as a coating solution, the spray mist size of the coating solution in a chamber of the fluidized bed was measured under various coating conditions, such as the distance from the spray nozzle, fluidization air volume, inlet air temperature and addition of sodium chloride (NaCl) into the coating solution. The mist size in the fluidized bed was compared with that in open air at various distances from the spray nozzle. Further, the relationship between the spray mist size and the degree of suppression of agglomeration at various NaCl concentrations during fluidized bed coating was studied. The mist size distribution showed a logarithmic normal distribution in both cases of the fluidized bed and open air. The number-basis median diameter of spray mist (D50) in the fluidized bed was smaller compared with that in open air. D50 increased with the increasing distance from the spray nozzle in both cases. In the fluidized bed, D50 decreased with the increasing fluidization air volume and inlet air temperature. The effect of NaCl concentration on the mist size was hardly observed, but the degree of suppression of agglomeration during coating increased with the increasing NaCl concentration in the coating solution.

Chemistry, Pharmaceutical↗

Joint Photographic Experts Group compression of intraoral radiographs for image transmission on the World Wide Web.

OBJECTIVE: The purpose of this study was to evaluate the subjective quality of Joint Photographic Experts Group (JPEG) compressed images of intraoral radiographs with file sizes of 30 kilobytes or less, which can be transmitted quickly on the World Wide Web. STUDY DESIGN: Conventional intraoral radiographs were digitized at sampling rates of 100, 200, 300, 400, and 600 dots per inch through use of a flatbed scanner and saved in JPEG format in 11 compression degrees. Fifty-five combinations of sampling rate and compression degree were evaluated by means of a visual analog scale. Sampling rate and compression degree combinations whose quality was inferior to that of an average image were excluded. The quality of the remaining combinations was subsequently evaluated through assessment of 8 anatomical features in each image. RESULTS: Forty of the 55 combinations provided a file size less than 30 kilobytes. Thirty combinations obtained VAS scores of 0 or higher on the standardized VAS. As a result, 16 combinations of sampling and compression conditions were selected for the second part of the study. Only one combination of sampling rate and compression degree was found to provide sufficient image quality for all 8 anatomical features. CONCLUSIONS: Under the file size limit of the study design, the full-sized compressed image of an intraoral radiograph did not always provide sufficient quality. This problem will be reduced by improvements in telecommunications infrastructure, which will permit faster transfer of files of larger size.

Algorithms↗

Suppression of agglomeration in fluidized bed coating. III. Hofmeister series in suppression of particle agglomeration.

PURPOSE: Fourteen kinds of salts consisting of various cations and anions in the Hofmeister series were used as additives for suppression of particle agglomeration in the fluidized bed coating. We attempted to clarify the relationship between the suppression effect of the salts and the Hofmeister series of their consistent ions. METHODS: Fluidized bed coating was carried out with hydroxypropylmethyl cellulose (HPMC) aqueous coating solution containing the salts and Celphere as core particles. To elucidate the salting-out power of the salts for HPMC, the transmittance of the coating solutions at 600 nm was measured at various temperatures and the phase separation temperature (T(PS)) was determined from the values at 50% transmittance. RESULTS: A high suppression effect was observed when the salts including high order ions in the Hofmeister series were added to the coating solution. T(PS) decreased in the presence of the salts except for sodium iodide and sodium thiocyanate and lowered with the higher order ion in the Hofmeister series. The particle agglomeration was suppressed with decrease in T(PS) of the HPMC aqueous coating solution. CONCLUSIONS: It has been suggested that the suppression effect of a salt on the particle agglomeration depended on the salting-out power of the salt. We regard sodium citrate and potassium citrate as very useful pharmaceutical additives for the suppression of particle agglomeration in actual pharmaceutical coating.

Algorithms↗

Detection of gene-environment interaction by case-only studies.

BACKGROUND: The detection of gene-environment interaction can provide important clues not only for resolving biological mechanisms underlying diseases, but also for disease prevention. The newly introduced case-only study was compared with traditional case-control study in terms of statistical power to detect significant gene-environment interaction. METHODS: Odds ratios for interaction were calculated in the framework of case-control study and case-only study separately, by an unconditional logistic model. Hypothetical data with 200 cases and 200 or 400 controls and real published data derived from four cancer case-control studies of genotype and smoking were used for the comparisons. RESULTS: Although odds ratio estimates for interaction were the same, 95% confidence intervals were narrower in case-only studies than in case-control studies. Similarly, there were no substantial differences in point estimates for interaction in four real cancer case-control studies between the two study designs, but the confidence intervals were narrower with the case-only study. CONCLUSIONS: Although the case-only study does not provide odds ratios for exposure or genotype alone, it is very useful for the detection of interaction, especially for screening purposes.

Case-Control Studies↗

Absorption of vitamin K2 by dogs after oral administration of a soft gelatin capsule formulation containing a new emulsion-type vehicle.

This study has evaluated the performance of a newly developed vehicle for administration of a drug in a soft gelatin capsule. The absorption of vitamin K2 in dogs after oral administration of the vitamin in a soft gelatin capsule containing the newly developed vehicle was compared with absorption after administration of a control formulation prepared by encapsulating the contents of a commercially available vitamin K2 capsule (Glakay capsules 15 mg) in the same type of soft gelatin. Under non-fasted conditions the profile of the plasma concentration of vitamin K2 against time for the test formulation was comparable with that for the control formulation in non-fasted dogs. Under fasted conditions, however, both the maximum concentration (Cmax) and the area under the plot of concentration against time (AUC) were significantly smaller for the test formulation than for the control formulation. The Cmax and AUC for the test formulation were about 10 times larger for non-fasted dogs than for fasted dogs whereas values for the control formulation were about twice as large. These results suggest that both formulations might require the presence of food or digestive fluid components, or both, for better absorption of vitamin K2. It seems that although the performances of the test and control formulations were comparable in the presence of these components, the control formulation works better in their absence. It should be also noted that, in contrast with the results from the absorption tests, the dispersibility of the test vehicle in water was much better than that of the control vehicle. This suggests that dispersibility does not significantly affect vitamin K2 absorption. In conclusion, although the new vehicle did not perform better than the control vehicle in terms of vitamin K2 absorption, the performance of the control formulation was comparable for non-fasted dogs. Because the new vehicle contains considerably less surfactant than the vehicles currently used in soft gelatin capsules, it could be a safer alternative for use under non-fasted conditions.

Administration, Oral↗

Emulsion type new vehicle for soft gelatin capsule available for preclinical and clinical trials: effects of PEG 6000 and PVP K30 on physicochemical stability of new vehicle.

To prevent temperature-dependent gel-sol transformation of an o/w emulsion type new vehicle system for a soft gelatin capsule, which may be available for both preclinical and clinical trials, the basic new vehicle formulation (PEG 400:purified water:medium chain triglyceride:polyoxyethylene (20) cetylether = 77:10:10:3) was modified by partially (1, 2 or 3%) replacing PEG 400 with PEG 6000 or PVP K30. When 2 or 3% of PEG 400 was replaced with PEG 6000, temperature-dependent gel-sol transformation was prevented at temperatures below 40 degrees C, and the vehicle appeared to be stable during 8 weeks of storage at 4 to 40 degrees C; the particle size distribution remained unchanged. When 1% of PEG 400 was replaced with PEG 6000, gel-sol transformation was not prevented, though phase separation was not observed at sol state, and the particle size distribution was shifted to be in a larger particle size range after 2 weeks of storage. When PEG 400 was partially (1, 2 or 3%) replaced with PVP K30, temperature-dependent gel-sol transformation was not prevented and, after 2 weeks of storage at 40 degrees C, the particle size distributions of the vehicles were shifted to be in a larger particle size range and the vehicles were separated into two layers. These results suggested that a small amount of PEG 6000 plays an important role in preventing temperature-dependent gel-sol transformation of our developed vehicle system.

Capsules↗

Immunohistochemical characteristics of estrogen receptor alpha positive cells in glandular epithelium of the rat seminal vesicle.

Epithelial cells of the rat seminal vesicle stained positively for nuclear estrogen receptor alpha (ER alpha). We studied these cells using immunohistochemical means. We demonstrated in a previous study that some glandular epithelial cells of the seminal vesicles of immature castrated rats treated with estrogen for 1-2 weeks had multilayer features. The present study shows that these glandular epithelial cells are nuclear ER and basal cell-specific cytokeratin (34betaE12) positive. These findings suggested characteristics of basal cells. Moreover, we demonstrated that these cells express transforming growth factor beta1 (TGFbeta1) as a result of castration and estrogen treatment. Our findings indicate that glandular epithelial cells with multilayer features, which stained positively for nuclear ER alpha have basal cell features and may play an important role in the expression of TGFbeta1 through an epithelial-stromal interaction.

Animals↗

Genetic analysis of a dentatorubral-pallidoluysian atrophy family: relevance to apparent sporadic cases.

Dentatorubral-pallidoluysian atrophy (DRPLA) is associated with an unstable CAG trinucleotide sequence. We describe a DRPLA family whose members have an allele containing an expanded CAG repeat, even in an elderly neurologically normal individual. The proband developed DRPLA at age 14. She was initially considered a sporadic case, but later her sister became symptomatic. Investigation of the number of CAG repeat units in her family revealed the 81-year-old father to have an expanded CAG repeat of 51 units. To our knowledge, such an advanced aged unaffected patient has not been previously documented. The present example may explain apparent sporadic cases.

Adult↗

[Completion pneumonectomy combined with graft replacement of thoracic aortic aneurysm by simple clamping].

A 59-years-old male patient who had left upper lobe partial resection 30 years ago. He was seen at the family physician because of cough. A chest X-ray was showing an abnormal mass shadow measuring 3 x 4 cm in left lower lobe like honey comb. And squamous cell carcinoma (SCC) was detected in his sputum. He was diagnosed as primary lung cancer and introduced to our department to have operation. Chest CT-scan was showing lung tumor suspected SCC measuring 4.3 x 2.6 cm in segment 8 faced chest wall. At the same time, we detected thoracic aortic aneurysm and subcarinal lymph node, but could not see where the boundary is, so it was hard to distinguish between parietal thrombus with thoracic aortic aneurysm and swelling subcarinal lymph node. We decided it swelling subcarinal lymph node by three-dimensional treated CT-scan. Aortic angiography was showing proximal descending aortic aneurysm measuring diameter was 4.5 cm. Abdominal CT-scan was showing infrarenal abdominal aortic aneurysm measuring diameter was 5.5 cm. He was diagnosed as primary lung cancer (It. S8, SCC) (cT2N2M0, Stage IIIB), thoracic aortic aneurysm, abdominal aortic aneurysm, and idiopathic pulmonary fibrosis, and had completion pneumonectomy (R 2 b) for primary lung cancer and graft replacement with aneurysm dissection for thoracic aortic aneurysm without extracorporeal circulation. In this operation, we could find swelling subcarinal lymph node measuring 5 x 3 cm instead of parietal thrombus with thoracic aortic aneurysm. Pathological examination diagnosed middle differential SCC and no metastasis from dissected lymph node (PT2N0M0, Stage I A).

Aorta, Thoracic↗

[Spinal anesthesia for a patient with long-term SMON].

SMON (subacute myelo-optico-neuropathy) may result from clioquinol neurotoxicity. An 81-year-old woman underwent internal fixation for left intertrochanteric fracture. She had been diagnosed as having SMON twenty years previously. Sensory examination revealed paresthesia and decreased deep sensation in the lower extremity. A recent neuropathological report shows that in long-term SMON of about fifteen years, degeneration is located from the medulla oblongata to T5-6. We performed spinal anesthesia of which the level of analgesia was below T5-6 in the present case. The level of anesthesia was determined by the pinprick test, and was recognized as below T10. Postoperatively, both the sensory level of analgesia and vital signs remained stable. There was no worsening of neurological findings after spinal anesthesia, including the postoperative period. In conclusion, spinal anesthesia which was limited to below the level of degeneration could be applied in a case of long-term SMON.

Aged↗

[Clinical comparison of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung for each case].

Because we experienced each 1 operative case of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung discovered with pleural effusion, clinical comparison investigated both. The first case was suspected diffuse malignant mesothelioma of the pleura before operation, and we performed pleuropneumonectomy. But the pathologic diagnosis was adenocarcinoma of the lung, what is so called pseudomesotheliomatous carcinoma. The second case had inhaled asbestos and his pleural effusion revealed high concentrations of hyaluronic acid. Thoracoscopic biopsy showed malignant mesothelioma, and we performed pleuropneumonectomy. The pathologic final diagnosis was diffuse malignant mesothelioma of the pleura. In clinical differential diagnosis of diffuse malignant mesothelioma of the pleura and pseudomesotheliomatous carcinoma of the lung, history of inhalation of asbestos and concentrations of hyaluronic acid in pleural effusion are helpful. And thoracoscopic biopsy is necessary in established diagnosis.

Adult↗

[Consent to enrollment in randomized clinical trials].

Multi-facility joint randomized clinical trials for cancer treatment are the most common method of current clinical study. However, the difference in the rate of participation in multi-facility randomized clinical trials may damage the resulting general validity. Therefore, we studied whether the rate of participation in randomized clinical trials is different between university hospitals and other general hospitals using a questionnaire (with anonymity preserved). There were 744 subjects from university hospitals and 339 from general hospitals participating in the study. The results showed that 10.9 percent of those from university hospitals were willing to participate, against 28.1 percent who were not. Of those from general hospitals (public hospitals in this study) 10.6 percent answered that they would participate and 27.4 percent that they would not. Little difference was found in the rate of participation in randomized clinical trials between university hospitals and other general hospitals. The focus is thus on doctors to solve the possible differences between the facilities in further multi-facility joint studies.

Adolescent↗

Solid phase synthesis of oligomannopeptoids that mimic the concanavalin A-binding trimannoside.

Oligomannopeptoids from the dimer to the hexamer were produced by solid phase synthesis and their abilities to bind to concanavalin A (ConA) were assessed. The assessment indicated similarity between the oligomannopeptoids and the naturally occurring oligomannosides in the enthalpy of the binding and the valence number vs binding strength relationship, encouraging the use of the oligomannopeptoids as oligomannoside mimics.

Binding, Competitive↗

Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor.

Protein C inhibitor (PCI) is the plasma serine protease inhibitor of activated protein C, the active enzyme of the anticoagulant protein C pathway. Recently, PCI was also detected in human seminal plasma and reproductive organs (testis, seminal vesicle and prostate) suggesting that PCI may also play an important role in the reproductive system. In this study, we cloned the full length of rat PCI cDNA, and determined its amino acid sequence and tissue distribution. We also evaluated the effect of androgen on PCI mRNA expression in seminal vesicles and testes. The isolated 2074-bp rat PCI cDNA was composed of a 47-bp 5'-non-coding region, a 1218-bp coding region of a 406-amino acid precursor protein, a stop codon and a 806-bp 3'-non-coding region. The deduced amino acid sequence of rat PCI showed 85.7%, 64.1% and 62.2% homology with that of mouse, rhesus monkey and human PCIs, respectively. Northern blot analysis showed that the rat PCI mRNA is expressed strongly in the seminal vesicle, moderately in the testis, but not in the liver. PCI mRNA expression in seminal vesicles and testes was found to increase during the process of development, suggesting that it is under androgen control. Subsequently, we examined the effect of castration and/or treatment with 17beta-estradiol or testosterone on PCI mRNA expression in the mature rat seminal vesicles. The PCI mRNA expression in seminal vesicles was significantly decreased after castration or 17beta-estradiol treatment. Testosterone itself did not affect PCI mRNA expression, but treatment in castrated rats significantly enhanced its mRNA expression. These findings suggest that the PCI gene expression in rat seminal vesicles is regulated by androgen.

Amino Acid Sequence↗

Synthesis of 5-thiomannose-containing oligomannoside mimics: binding abilities to concanavalin A.

5-Thiomannose-containing oligomannoside mimics, 5SMan alpha(1,6)Man, 5SMan alpha(1,3)Man, 5SMan alpha(1,6)¿Man alpha(1,3)Man¿, Man alpha(1,6)¿5SMan alpha(1,3)Man¿, and 5SMan alpha(1,6)¿5SMan alpha(1,3)Man¿, were synthesized. Dissociation constants for the binding of these mimics to concanavalin A (ConA) were determined by a fluorescence anisotropy inhibition assay. Comparison of these data with those of the natural oligomannosides and with a crystal structure of the trimannoside-ConA complex established that replacing a ring oxygen atom with a sulfur atom causes about 1 kcal/mol decrease in the binding free energy when the ring oxygen is recognized with a hydrogen bonding.

Concanavalin A↗

Physiological mechanism-based analysis of dose-dependent gastrointestinal absorption of L-carnitine in rats.

We evaluated the dose-dependent (saturable) gastrointestinal absorption of L-carnitine, a lipid-lowering agent, in rats by a physiological mechanism-based approach to clarify its absorption characteristics and to examine the in vitro (in situ)-in vivo correlation in intestinal transport. The intestinal absorption rate constant (ka), which was estimated by the analysis of gastrointestinal disposition, decreased markedly from 0.1061 to 0.0042 min(-1) when the dose was increased from 0.05 micromol rat(-1) (low dose) to 100 micromol rat(-1) (high dose). The dose-dependence in ka was attributable to the saturability of intestinal transport that, in the perfused intestine, was similar to the saturability in ka. At the high dose, the apparent absorption rate constant (k'a) of 0.0021 min(-1), which was estimated by the analysis of plasma concentrations after oral administration, was an order of magnitude smaller than the gastric emptying rate constant (kg) of 0.059 min(-1) and comparable with the ka of 0.0042 min(-1), suggesting that the gastrointestinal absorption of L-carnitine is absorption-limited in the intestine. At the low dose, where intestinal L-carnitine absorption was far more efficient, the k'a of 0.0172 min(-1) was smaller than the ka of 0.1061 min(-1) and closer to the kg of 0.072 min(-1), suggesting that apparent absorption was retarded by gastric emptying which is less efficient than intestinal absorption. This shift in the rate-determining process with an increase in dose explains the less marked dose dependence in k'a compared with ka. The bioavailability decreased from 100 to 42% with an increase in dose. This could be accounted for quantitatively by a reduction in the fraction absorbed (F(a,oral)) due to a reduction in ka, assuming first-order absorption during the transit time of T(si) through the small intestine (F(a,oral) = 1 - exp(-ka x T(si))). Thus, using L-carnitine as a model, this study has successfully demonstrated that the saturability in gastrointestinal absorption can be correlated with the intestinal transport in a quantitative and mechanism-based manner. This should be of help not only for developing more efficient oral L-carnitine delivery strategies, taking advantage of in vitro (in situ) information about the intestinal transport mechanism, but also for establishing a more generally applicable in vitro (in situ)-in vivo correlation in gastrointestinal absorption.

Algorithms↗

A mathematical model of adaptive behavior in quadruped locomotion.

Locomotion involves repetitive movements and is often executed unconsciously and automatically. In order to achieve smooth locomotion, the coordination of the rhythms of all physical parts is important. Neurophysiological studies have related that basic rhythms are produced in the spinal network called, the central pattern generator (CPG), where some neural oscillators interact to self-organize coordinated rhythms. We present a model of the adaptation of locomotion patterns to a variable environment, and attempt to elucidate how the dynamics of locomotion pattern generation are adjusted by the environmental changes. Recent experimental results indicate that decerebrate cats have the ability to learn new gait patterns in a changed environment. In those experiments, a decerebrate cat was set on a treadmill consisting of three moving belts. This treadmill provides a periodic perturbation to each limb through variation of the speed of each belt. When the belt for the left forelimb is quickened, the decerebrate cat initially loses interlimb coordination and stability, but gradually recovers them and finally walks with a new gait. Based on the above biological facts, we propose a CPG model whose rhythmic pattern adapts to periodic perturbation from the variable environment. First, we design the oscillator interactions to generate a desired rhythmic pattern. In our model, oscillator interactions are regarded as the forces that generate the desired motion pattern. If the desired pattern has already been realized, then the interactions are equal to zero. However, this rhythmic pattern is not reproducible when there is an environmental change. Also, if we do not adjust the rhythmic dynamics, the oscillator interactions will not be zero. Therefore, in our adaptation rule, we adjust the memorized rhythmic pattern so as to minimize the oscillator interactions. This rule can describe the adaptive behavior of decerebrate cats well. Finally, we propose a mathematical framework of an adaptation in rhythmic motion. Our framework consists of three types of dynamics: environmental, rhythmic motion, and adaptation dynamics. We conclude that the time scale of adaptation dynamics should be much larger than that of rhythmic motion dynamics, and the repetition of rhythmic motions in a stable environment is important for the convergence of adaptation.

Adaptation, Physiological↗