Biomedical subjects

H Sato

Publications and source records attributed to H Sato.

At least 235 records · Page 13Linked to original sources

PubMed2001

Pharmacokinetic and pharmacodynamic analysis of the antihypercalcemic effect of incadronate disodium in rats.

Incadronate concentrates into the bone as a target organ after intravenous administration of incadronate disodium. Mature osteoclasts has take up incadronate from the bone surface and convert it from an active to an inactive form. As a result, incadronate decreases the plasma calcium concentration by suppressing bone resorption. In this study, the pharmacokinetic and pharmacodynamic (PK/PD) analysis model for ascertaining the antihypercalcemic effects of incadronate disodium was developed in rats. Data on both the concentration of incadronate in bone and that of free calcium in blood after intravenous administration from our previous study were used for analysis. To estimate the concentration in the surface layer of bone, data on the concentration of incadronate in bone after single intravenous administration were analyzed based on the PK model considering three-compartments. The estimated concentrations in the surface layer in bone were applied to the PD model as an input function. The PD model was developed to analyze the changes in the plasma calcium concentration after a single intravenous administration considering an irreversible inhibition of osteoclast activity. The obtained fitted curves were in good agreement with the observed data. The model could explain the long duration of the antihypercalcemic effect of incadronate disodium and should be useful for planning rational dose regimens for effective antihypercalcemic therapy.

Animals↗

PubMed2001

A comparative pharmacodynamic study of the arrhythmogenicity of antidepressants, fluvoxamine and imipramine, in guinea pigs.

Among several classes of antidepressants, tricyclic antidepressants are known to prolong QTc intervals (QT interval corrected by heart rate) in electrocardiograms, while selective serotonin uptake inhibitors (SSRI) are considered to be devoid of arrhythmogenicity. In this study, we aimed to compare the arrhythmogenic potencies of imipramine (IMI), a typical tricyclic antidepressant, and fluvoxamine (FLV), an SSRI, at therapeutic and supratherapeutic concentrations using guinea pigs in vivo. Guinea pigs were anesthetized, and IMI (10 and 20 mg/kg/h) or FLV (20 mg/kg/h) was intravenously administered for 90 minutes to obtain the time-courses of drug concentrations in plasma and the changes in the QTc intervals during and after the drug administration. IMI induced distinct QTc prolongation in a dose-dependent manner, while FLV prolonged QTc intervals only slightly. A pharmacokinetic-pharmacodynamic analysis revealed that the potency for QTc prolongation of IMI was 1.7-fold higher than that of FLV. Taking the therapeutic concentration into account, the clinical risk of FLV for QTc prolongation was suggested to be 5-fold lower than that of IMI. Therefore, this SSRI agent was suggested to be safer than the tricyclic antidepressant for patients with cardiac risk factors, including arrhythmia, or for those taking other arrhythmogenic drugs concomitantly.

Animals↗

PubMed2001

Practical synthesis of a 1beta-methylcarbapenem, J-111,225, using 4-mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine as a precursor.

An effective and practical procedure for the synthesis of J-111,225 (1), a new 1beta-methylcarbapenem, was developed using 4-mercapto-2-14-(N-methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction of 2a with p-nitrobenzyl (PNB)-protected 1beta-methylcarbapenem enolphosphate 3a and successive removal of PNB group afforded J-111,225 (1) in significantly increased yield compared to the ordinary procedure using a C-2 side-chain thiol with amino-protective groups.

Anti-Infective Agents↗

PubMed2001

The chemistry of indoles. CIII. Simple syntheses of serotonin, N-methylserotonin, bufotenine, 5-methoxy-N-methyltryptamine, bufobutanoic acid, N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine, and lespedamine based on 1-hydroxyindole chemistry.

Application of regioselective nucleophilic substitution reactions of 1-hydroxytryptamines to novel and simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a), bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported.

Alkaloids↗

PubMed2001

[Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection].

Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively. The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5. The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection. In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min). In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration. However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks. The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C. Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80%. Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM. The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective. After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved. On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view. It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.

Aged↗

PubMed2001

[The roles of pharmacists on prior review of clinical trials].

A prior review system for clinical trials was introduced into The University of Tokyo Hospital in March 1999, for the purpose of supporting the Institutional Review Board (IRB). In this study, we investigated the effect of this system on IRB, and evaluated roles of pharmacists involved in utilizing this prior review system. An average period from the acceptance of regular application of each protocol to the approval of IRB was 1.7 months, and the period was significantly shorter than that before the introduction of this system (2.3 months). On the other hand, the number of instructions given to applicants increased to be 2.8 times before the introduction of this system, suggesting the improvement of the quality of this prior review system. In the prior review, the number of instructions pointed out from pharmacists concerning pharmacokinetics, pharmacodynamics, drug-interactions, adverse reactions, and the other matters related to investigational drugs was greater than that from doctors or nurses. According to the results of the surveys for doctors, nurses, and other clerical employees, pharmacists were indicated to review from a pharmaceutical point of view and their review was found to be very important. In conclusion, the prior review system was considered to be useful for the rational practice of clinical trials and pharmacists were recognized to be indispensable as reviewers on the prior review.

Clinical Trials as Topic↗

PubMed2001

[Development of an inspection-supporting system using drug images for unit dose packages].

When inspecting unit-dose packaged drugs, there would be some possibility of inspection errors and ultimately dispensing errors due to pharmacist's incorrect memory of drug identification. Therefore, this study was aimed to establish a computer-aided system for inspecting drugs of unit dose packages more accurately and efficiently. First, we analyzed the identifiability of 5846 tablets and capsules using drug codes, in order to define an identification problem for unit dose-packaged drugs. It was shown that as much as 36% of the drugs do not have any codes, 4.0% of the code-marked drugs have identical codes with others, and that 9.7% of the drugs with codes on both sides of the surface share the same code with other drugs. Thus, it was clearly shown that in many cases it is impossible to identify pharmaceuticals exactly using drug codes only. On the other hand, it was indicated that approximately 80% of the drugs which were not identified with drug codes only, could be identified when additional information on drugs' color, size, form, and splitting line was provided. Therefore, in this study, we designed an inspection-supporting system to present promptly all the information necessary for the drug identification by displaying real drug images as linked with prescribing information on the monitor. Retrieval of prescription data from the order entry host was automatically performed by entering patient's ID number or by selecting a patient from the name list of patients at the inspection terminal computer. Moreover, the system was equipped with abilities to automatically check drug interactions and duplicate prescriptions, to provide various information of prescribed drugs and to monitor patients' drug history. We used the developed system and evaluated that it is a useful tool for accurate and efficient inspection of unit dose-packaged drugs. In addition, the quality of drug inspection increased by utilizing system functions such as checking drug interactions and providing drug information.

Clinical Pharmacy Information Systems↗

PubMed2001

Association of seropositivity for antibody to Chlamydia-specific lipopolysaccharide and coronary artery disease in Japanese men.

Recent studies suggest an association between Chlamydia pneumoniae infection and coronary artery disease (CAD). To examine this relationship in Japanese men, serum IgA and IgG antibodies to Chlamydia-specific lipopolysaccharide were measured by enzyme-linked immunosorbent assay in 507 patients with CAD and 200 age-matched controls. CAD patients were divided into (1) 269 patients with myocardial infarction (MI) and (2) 238 patients with chronic coronary heart disease (CCHD). Compared with the control group, the CAD group did not differ in the prevalences of both antibodies (IgA: 23.7 vs 18.0%, p=0.10; IgG: 52.7 vs 51.0%, p=0.6). The index of IgG antibody was not significantly different between CAD and control groups (median 1.19 vs 1.18, p=0.3), whereas the index of IgA antibody was significantly higher in CAD than control group (median 0.60 vs 0.46, p<0.0001). Compared with the control group, the MI group had a significantly higher prevalence of IgA antibody (28.6 vs 18.0%, p=0.007); however, there was no difference in the prevalence of IgG antibody (58.0 vs 51.0%, p=0.13). The CCHD group did not differ in the prevalences of both antibodies (IgA: 18.1 vs 18.0%, p=0.9; IgG: 45.6 vs 51.0%, p=0.2). After the adjustment for coronary risk factors, odds ratios (ORs) of seropositive antibodies for CAD were 1.59 [95% confidence interval (CI): 0.88-2.87, p=0.12] for IgA seropositivity and 0.92 (95%CI: 0.58-1.47, p=0.7) for IgG seropositivity in all cases. In the MI and control groups, ORs of seropositive antibodies for MI were 2.67 (95%CI: 1.32-5.38, p=0.007) for IgA seropositivity, and 1.36 (95%CI: 0.79-2.36, p=0.2) for IgG seropositivity. This study discovered that IgA antibody to Chlamydia was significantly associated with CAD, especially with MI, in Japanese Men and the findings suggest that chronic infection of Chlamydia may be linked to the pathogenesis of MI.

Aged↗

PubMed2001

Circadian variation of the onset of acute myocardial infarction in the Osaka area, 1998-1999: characterization of morning and nighttime peaks.

The onset of acute myocardial infarction (AMI) shows characteristic circadian variations; that is, a definite morning peak related to biologic rhythms and a vague nighttime peak related to socioeconomic factors. The recent economic recession in Japan may change the circadian variation, especially the nighttime peak. This study evaluated the recent circadian variation of AMI in Osaka and specified the patient subgroups showing either a morning or nighttime peak predominantly. Of 1,609 consecutive patients with AMI registered from April 1998 to January 2000, 1,252 whose onset of AMI was definitely identified were studied. The day was divided into six 4-h periods with a morning peak between 08.01 h and 12.00h, and nighttime peak between 20.01 h and 24.00h. When subgroup analysis was performed, female patients aged 65 years or more showed a morning peak alone and male patients aged less than 65 years with an occupation and the habits of cigarette smoking and alcohol intake showed a nighttime peak alone. Thus, in Osaka nighttime socioeconomic factors may currently be more potent triggers of AMI than the morning surges in younger male workers who smoke and drink.

Adult↗

PubMed2001

Purification and properties of extracellular chitinases from the parasitic fungus Isaria japonica.

Two chitinases (P-1 and P-2) induced with colloidal chitin were purified from the culture supernatant of Isaria japonica by chromatography on DEAE Bio-Gel, chromatofocusing and gel filtration with Superdex 75 pg. The enzymes were electrophoretically homogeneous and estimated to have a molecular mass of 43,273 (+/-5) for P-1 and 31,134 (+/-6) for P-2 by MALDI-MS. The optimum pH and temperature was 3.5-4.0 and 50 degrees C for P-1 and 4.0-4.5 and 40 degrees C for P-2. P-1 acted against chitosan 7B (degree of deacetylation, 65-74%) = glycol chitin > colloidal chitin = chitosan 10B (degree of deacetylation, above 99%) and P-2 against chitosan 7B > glycol chitin = chitosan 10B > colloidal chitin in order of activity. The products of hydrolysis of chitin and chitosan hexamer were analyzed by MALDI-MS. The products from the chitin hexamer obtained with P-1 were almost all dimers with only a small amount of trimer whereas those obtained with P-2 were mainly trimers with some dimer and tetramer. No hydrolysis of chitosan hexamer was observed. High homology in the amino-terminal sequence for chitinase P-1 was exhibited by chitinases from Trichoderma harzianum, Candida albicans and Saccharomyces cerevisiae in the range of 48-39%. The highest homology for Chitinase P-2 was shown by an endochitinase from Metarhizium anisopliae of 66%, while 44% homology was exhibited by chitinases of Leguminosae plants.

Journal Article↗

PubMed2001

[Policy science and health policy].

Policy science provides the analytical frameworks to examine (1) the process of policy formation and implementation (Issue definition, Agenda setting, Alternative development, Decision and implementation, and Appraisal); (2) the initial and final shapes of policy content (Temporal and special distribution of costs and benefits, Selection of administrative organizations, and Choice of instruments to secure policy compliance); and (3) the effects and efficiencies of policy (Expected and unexpected effects of policy, beneficial and adverse ones). These three aspects are closely associated, and determine the functions of policy in society. Overseas, the application of policy science framework to health issues has thus far produced substantive knowledge which helps to improve both the policy making and policy designs, and at the same time, has provided good opportunities on which the workings of health and policy, both at the social and individual levels, are explored. The paper first outlines the themes and frameworks of political science, and then, introduces their application to the field of health. Issues associated with human life and health have special characteristics that distinguish them from those of other market commodities: special values placed on life and health, information inequality between service providers and consumers, and externalities, leading to a variety of moral hazards and market failures. Furthermore, there are some conflicts in values and technical opinions in society, regarding both the ends and means of health policies. In addition to the main topics in the field, empirical studies, from Japan or from other countries, are also summarized. Finally, future research needs and expectations are addressed.

Efficiency, Organizational↗

PubMed2001

(-)-Semivioxanthin, a new abscisic active compound against Hinoki cypress leaves isolated from Cryptosporiopsis abietina.

The new naphthopyrone, (-)-semivioxanthin (1) was isolated from Cryptosporiopsis abietina. The structure of 1 was determined as the reversed optical isomer of semivioxanthin by comparing its spectroscopic data with those of semivioxanthin. Compound 1 exhibited abscisic activity against Hinoki cypress leaves and antifungal activity against Cladosporium herbarum.

Abscisic Acid↗

PubMed2001

Bronchoalveolar lavage for the diagnosis and treatment of pneumonia associated with transport in Thoroughbred racehorses.

To evaluate a hypothese that use of bronchoalveolar lavage (BAL) for early treatment of pneumonia would improve their prognosis by reducing bacterial numbers and excessive numbers of neutrophils in the lung, initial experiences with BAL in the diagnosis and treatment of pneumonia were performed in 36 racehorses that became ill within 24 hr of long distance travel (1,200-1,600 km, 26-32 hr) by road. Comparisons were made of the outcomes of the 36 horses and those of 42 horses (81.0% recovered, 50.0% returned to racing) treated for transport associated pneumonia without BAL. The total amount of BAL fluid injected during hospitalization varied from 700 to 3,700 ml and the duration of antibiotic treatments ranged from 5 to 40 days. Clinical symptoms after lavages showed good results with no side effects. None of the horses required thoracic drainage. Horses treated with BAL required shorter period of antibiotic therapy, a greater percentage recovered (100%, 36/36) and a greater percentage returned to racing (77.8%, 28/36). Eight (22.2%) never raced because of lameness or other considerations.

Animals↗

PubMed2001

Effects of enterostatin (Val-Pro-Asp-Pro-Arg) on fat intake and blood levels of glucose and insulin in rats.

Enterostatin may be involved in the preference for fat and the control of fat intake. Using two different feeding patterns, we observed a change in food intake after injection of enterostatin (VPDPR) into the third ventricle. When rats were adapted to free selection choice between low fat (LF) and high fat (HF) diets, VPDPR inhibited intake of the LF diet at 100, 200 and 800 ng and inhibited intake of the HF diet at 200 ng. The dose-response of HF diet intake to VPDPR was U-shaped. However, even the optimal dose (200 ng), which reduced the intake of both LF and HF diets when both diets were given together, was not effective when the LF diet was given alone. In the present study, VPDPR has also shown to not affect plasma glucose or insulin levels. These results suggest that exogenous VPDPR may inhibit appetite when endogenous enterostatin secretion is increased by ingestion of dietary fat, and that VPDPR has a limited range of effects on feeding behavior. We support the hypothesis that the early satiety sense of VPDPR as an anorectic agent in a central site is directly related to endogenous enterostatin or procolipase levels after fat intake, but not glucose or insulin levels.

Animals↗

PubMed2001

Age-related changes in the concentrations of major and trace elements in the brain of rats and mice.

Age-related changes in the concentrations of constituent elements in the brains of rats and mice 1 wk to 24 mo old were determined with inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). Seventeen elements could be determined with reasonable accuracy and reproducibility. They were P, K, Na, Mg, Ca, Fe, Zn, Cu, Rb, Al, Mn, Sr, Mo, Co, Pb, Cs, and Cd in order of concentrations in the adult rat brains. In these elements, six major elements (P, K, Na, Fe, Mg, Ca) were determined with ICP-AES and the others with ICP-MS. The concentrations of each element and the pattern of age-related changes were similar between the rat and mouse brains. The elements of which concentrations decreased with aging were K and Rb. On the other hand, the concentrations of some metal elements, including Fe, Cu, Sr, and Co, appeared to increase with growth and aging. The concentrations of other elements were relatively constant throughout the age examined.

Aging↗

PubMed2001

Predictive risk factors for pulmonary oxygen transfer in patients undergoing coronary artery bypass grafting.

UNLABELLED: The ratio of arterial oxygen tension to inspired oxygen fraction (PaO2/FiO2) is a useful indicator for weaning patients from mechanical ventilation and a reliable predictor of pulmonary dysfunction after cardiac surgery. The aim of this study was to elucidate the patient characteristics and variables that affect the PaO2/FiO2 ratio. Between 1994-1998, 167 patients who underwent coronary artery bypass grafting (CABG) were examined retrospectively. Spearman's correlation coefficients were calculated between the PaO2/FiO2 ratio and intubation period, and length of ICU stay. Patients were then divided into two groups with a PaO2/FiO2 ratio < 350 and PaO2/FiO2 ratio > or = 350. Univariate analysis of the putative risk factors was performed. A logistic regression model was developed to evaluate factors that would influence the PaO2/FiO2 ratio. A significant correlation was observed between the PaO2/FiO2 ratio and intubation period, and length of ICU stay. Univariate predictors of a PaO2/FiO2 ratio < 350 were low body weight, low preoperative PaO2 long operation time, high FiO2, low postoperative PaO2 history of smoking, hypertension and opening of pleura (p < 0.05). Excellent prediction was found with a model consisting of preoperative PaO2 and hypertension. CONCLUSION: The results of this study suggest that patients with a low preoperative PaO2 or hypertension may need more careful peri- and postoperative management since these factors are closely associated with the PaO2/FiO2 ratio.

Adult↗

PubMed2001

Microbiological contamination in genetically modified animals and proposals for a microbiological test standard for national universities in Japan.

The Biosafety Committee of the Japanese Association of Laboratory Animal Facilities of National Universities (JALAN) investigated recent episodes of microbiological contamination in genetically modified mice (GMM), and the countermeasures taken when the contaminated GMM were introduced into animal facilities, by questionnaires addressed to 53 animal facilities belonging to JALAN and serological tests. Although almost all of the contaminated GMM were accepted with conditions such as rederivation after or before reception and housing in designated rooms, contamination with a spectrum of microorganisms was demonstrated in GMM transferred domestically and from abroad. In serological tests, Mycoplasma pulmonis, mouse parvovirus, and mouse encephalomylitis virus were detected in GMM transferred from domestic facilities and from abroad. The present results of the questionnaires and serological tests suggest that GMM are highly and widely contaminated with microorganisms compared with mice from commercial breeders. Thus, we propose a microbiological requirement, including microbiological status--excellent, common, and minimum--as a guide for the transfer and procurement of mice and rats in Japan.

Animals↗

PubMed2001

The intensely positively charged perineuronal net in the adult rat brain, with special reference to its reactions to oxine, chondroitinase ABC, hyaluronidase and collagenase.

Light microscopic observations of healthy adult rat brain sections stained with anionic iron colloid indicated that 5-10% of neurons in the hippocampal subiculum and all neurons in the medial cerebellar nucleus possessed an intensely positively charged perineuronal net. This net was demonstrated to react to oxine, and therefore suggested to consist of guanidino compounds. It was further shown that the intensely positively charged perineuronal net, in accordance with the intensely negatively charged perineuronal net of proteoglycans, was digested by chondroitinase ABC, hyaluronidase, and collagenase, but not by endo-alphaN-acetylgalactosaminidase. This finding suggested that the former positively charged net might be linked to the latter negatively charged one.

Animals↗