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Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 451 records · Page 25Linked to original sources
PubMed1989

Studies on topical antiinflammatory agents. I. Synthesis and vasoconstrictive activity of corticosteroid 17-succinyl esters.

A series of 17-succinyl derivatives of four corticosteroids was prepared. They were tested for vasoconstrictive activity in humans, using 9 alpha-fluoro-11 beta, 21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV) as a standard. The activities of the 21-chloro 17-methylsuccinate compounds (6A, 6C and 6D) were greater than that of BV. A structure-activity relationship study showed that the activities of the 21-chloro 17-methylsuccinates were more potent than those of the corresponding 21-esters.

Administration, Topical↗
PubMed1989

Studies on topical antiinflammatory agents. II. Synthesis and vasoconstrictive activity of 21-substituted corticosteroids with sulfur-containing moieties.

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeroyloxy-1,4- pregnadiene-3,20-dione (betamethasone 17-valerate, BV).

Administration, Topical↗
PubMed1989

Studies on topical antiinflammatory agents. III. Synthesis of 17 alpha-acyloxy-9 alpha-fluoro-11 beta-hydroxy-16 beta-methyl-1,4-pregnadiene-3,20-dione 21-thio derivatives and related compounds.

A series of 21-thio derivatives of 9 alpha-fluoro-11 beta,17 alpha-dihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).

Administration, Topical↗
PubMed1989

Clinical evaluation of population pharmacokinetic parameters in phenytoin dosage adjustment.

We investigated the influence of the population pharmacokinetic parameters on the performance of the Bayesian feedback method in predicting the phenytoin (PHT) dosage needed to achieve a desired PHT serum concentration. Population pharmacokinetic parameters studied were taken from reports by Sheiner et al. (I), Grasela et al. (II), Miller et al. (III), and the authors (IV). The predictive abilities of the Bayesian feedback method were evaluated by using retrospective data from 70 patients. The mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) served as measures of prediction bias and precision. The precision of the initial estimates based on the population parameter set IV was superior to those of other initial estimates studied. The performance of the Bayesian feedback method to predict PHT dosage at the steady state was relatively insensitive to bias in the estimates of the population parameters. However, the revised estimates derived from the Bayesian feedback method using the population parameter set IV with one feedback gave the lowest MAE and RMSE in predicting PHT dosage.

Adult↗
PubMed1989

Development of Babesia ovata in the midgut of the tick, Haemaphysalis longicornis.

Studies were made on the development of Babesia ovata in the midgut of the nymphal tick vector, Haemaphysalis longicornis. In 12 hr post-repletion, merozoites were observed outside of erythrocytes infected with B. ovata in the contents of the midgut of the tick. After that, these merozoites were transformed into ring-forms which were comparatively large ring 2-3 microns in diameter. Within 48-72 hr post-repletion, ring-form protozoa developed into spherical form 4-5 microns in diameter. Within 3-4 days post-repletion, fission-forms were transformed into fission-bodies 2-3 microns in diameter. Within 4-6 days post-repletion, fission-bodies developed into bizarre-forms 6-7 microns in diameter. At this time, elongated form protozoa which were considered as microgametes, 6-8 microns in length, are also seen. Within 6-8 days post-repletion, round-formed protozoa which were considered as zygotes in 9-10 microns in diameter were observed in the gut. About 10 days after repletion, those round-formed protozoa were transformed into vermicule-formed and round-formed protozoa, 13-15 microns in length, appeared again in the gut epithelial cells.

Animals↗
PubMed1989

[Molecular composite resins reinforced with polyaramides (Part 1). Molecular interaction between N-Octylated-Poly-p-Phenylene Terephthalamide (PPTA) as core molecule and PMMA and Polystyrene (PS) as matrices].

Molecular composite PMMA resin (Oct-PPTA-PMMA) can be reinforced with poly-N-octyl-p-phenylene terephthalamide (Oct-PPTA) as rigid core molecule. Compounding 3 wt% of Oct-PPTA to PMMA increased compressive, diametral and bending strength by 10 to 15%. The molecular interaction between Oct-PPTA as the core molecule and PMMA as a polar matrix and polystyrene (PS) as a non-polar matrix was examined with respect to dynamic viscoelasticity. Compounding 3 wt% of Oct-PPTA (Oct-PPTA-PS) to PS decreased compressive, diametral and bending strength by 15 to 30%. The dynamic storage modulus (G') value of Oct-PPTA-PS is lower than G' of PS in the region from rubbery state to viscous flow state. These results reveal a significant effect of the polar groups on the molecular interaction between the core molecule and matrices in the molecular composites compounding Oct-PPTA as core molecule.

Chemical Phenomena↗
PubMed1989

[Clinical evaluation of Parkinson's disease using 123I-IMP SPECT].

N-isopropyl-p[123I]iodoamphetamine (123I-IMP) SPECT and regional cerebral blood flow (rCBF) studies were performed in 20 patients with Parkinson's disease (PD) and 8 normal subjects. RCBF was measured by the arterial blood sampling method which used the microsphere model. We analyzed seven factors which might be related to the rCBF in PD, i.e., age, stage, duration of the disease, cerebral atrophy, severity of dementia, laterality of symptoms and motor disability score (MDS; the degree of akinesia, rigidity, tremor, gait disturbance, freezing and pulsion sign). Compared with normal subjects, global CBF (supratentorial mean rCBF) was reduced 21.8% in PD. In particular, rCBF in the basal ganglia and that of frontal cortex were reduced 25.3%, 24.8%, respectively. Distribution patterns of rCBF in PD were almost as same as those in normals except for cerebellum. The reduction of both rCBFs in the basal ganglia and parietal cortex significantly correlated with MDS (p less than 0.05, respectively). Especially, akinesia was closely correlated to the reduction of rCBF in the parietal cortex (p less than 0.02). Moreover, we observed a significant relationship between cerebral atrophy and reduction of rCBF in each region except for cerebellum. However, there was no significant correlation between the severity of dementia and reduction of rCBF, even in the frontal cortex or parietal cortex. These data show that the severity of dementia in PD may be connected with other factors except for rCBF. 123I-IMP SPECT study is a useful method for clinical evaluation of PD.

Aged↗
PubMed1989

[A case of pulmonary alveolar proteinosis accompanied with the elevation of CEA (carcinoembryonic antigen) in bronchoalveolar lavage fluid].

A 44-year-old man was admitted with increasing dyspnea and butterfly shadow on his chest roentgenogram. Both the bronchoalveolar lavage and transbronchial lung biopsy (TBLB) led to a diagnosis of pulmonary alveolar proteinosis. CEA level in his bronchoalveolar lavage fluid (BALF) (216.8 ng/ml) was markedly elevated more than that in his serum (50.6 ng/ml). The localization of CEA on TBLB specimen stained by peroxidase-antiperoxidase technique using anti-CEA antibody was investigated and it was found that some alveolar epithelial cells and the material filling the alveoli were positively stained. Functions of alveolar macrophages in BALF were also studied, that is, adherence to glass, cell spreading, the nitroblue tetrazolium reduction, phagocytosis of immunobeads, and the activity of lysosomal enzymes, and found that all of those functions were lower than that of normal smokers. It was suggested that type II alveolar epithelial cells were those which produced and secreted CEA into the alveoli, as they do surfactant-like material in pulmonary alveolar proteinosis, and that the dysfunction of alveolar macrophages was secondary to the overingestion of the proteinaceous material in the alveoli.

Bronchoalveolar Lavage Fluid↗
PubMed1989

Development of Babesia ovata in the haemolymph of the tick, Haemaphysalis longicornis.

The haemolymph of adult tick Haemaphysalis longicornis (H. longicornis) infected with Babesia ovata (B. ovata) was examined at regular intervals. As a result kinetes could be detected in the haemolymph 15 days after engorgement. The kinetes detected could be classified into three types on the basis of their morphological characteristics. They increased gradually in number, reaching a maximum 23 days later. Then they tended to decrease in number, disappearing almost completely from the haemolymph 38 days after the engorgement of ticks.

Animals↗
PubMed1989

[Usefulness of ceftazidime in intractable respiratory tract infections].

Usefulness of ceftazidime (CAZ) was studied in 56 cases of intractable respiratory tract infections. CAZ was administered at a daily dose of 2-4 g in 2 divided doses by intravenous drip infusion for 3-15 days. 1. Analysis was carried out in 38 cases and the following result was obtained. Efficacy rate was: 68% (17/25) in pneumonia, 60% (3/5) in chronic bronchitis and 67% (4/6) in secondary infections in chronic respiratory disease cases, and the overall efficacy rate was 63.2% (24/38). 2. In bacteriological study, 68.2% (15/22) of eradication rate was obtained. Against Staphylococcus aureus, eradication was obtained in all strains (4 strains). Against Pseudomonas aeruginosa, eradication occurred in 4 strains out of 10, and decrease in number in 2 strains. 3. As for adverse effects, mild hepatic disorder was observed in 2 cases (3.6%) out of 56. 4. From the above result, CAZ is considered to be very useful when used as monotherapy for aged patients and in the treatment of severe and intractable infections accompanied by underlying diseases.

Aged↗
PubMed1988

Severe hypoplasia of lymphoid tissues in Mo1 deficiency.

A lymph node was examined from a 4-year-old female child with documented "Mo1" (CR3) deficiency. There was hypoplasia of the lymph node, with small, poorly delineated germinal centers and overall lymphopenia. Retrospective analysis of the clinical course of a decreased elder sister of the index patient indicated that the elder sister probably also had "Mo1" deficiency. Review of findings at autopsy revealed severe hypoplasia of all lymphoid organs with lymphopenia. Our observations suggest that lymphoid tissue hypoplasia may be a feature of CR3 deficiency and is likely a result of the defective lymphocyte adherence functions to endothelium associated with absent lymphocyte function-associated antigen (LFA-1).

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Comparison of single-point phenytoin dosage prediction techniques.

To dose the anticonvulsant phenytoin (PHT) in a clinical situation is difficult because of the non-linear metabolism of the drug. Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss). We retrospectively investigated six methods in a population of 130 out-patients treated with PHT. The dose needed to achieve a desired PHT concentration at ss was calculated based on an observed ss dose-concentration pair using a Bayesian feedback method (B), the Richens and Dunlop nomogram (RD), the Rambeck nomogram (R), the Martin nomogram (M), a population clearance equation (PC), and the Wagner equation (W). The mean prediction error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MEs for B, RD, R, M, PC, and W, respectively, were -0.4, 1.2, 6.9, 3.4, -1.8, and 0.0 mg/day. The MAEs were 33.9, 38.5, 44.3, 50.4, 43.5, and 53.7 mg/day. The RMSEs were 43.7, 53.1, 65.2, 63.5, 56.0, and 68.2 mg/day. The MAE and RMSE showed lowest values for method B, followed by method RD. Therefore, we assume that method B is the most accurate in making routine PHT dosage adjustments.

Adolescent↗
PubMed1988

The Effect of Diminazene Aceturate on Spienectomized Dogs with Babesia gibsoni Infection.

The effect of diminazene aceturate on splenectomized and nonspienectomized dogs with Babesia gibsoni (B. gibsoni) infection was investigated. In splenectomized dogs, the fissional and multiplicational stages of B. gibsoni were observed in peripheral blood films, and hemoglobinuria was frequently observed. These findings were different from previous reports and were not changed by administration of diminazene aceturate. It is clear that the intramuscular administration of diminazene aceturate at the dose of 3 mg/kg body weight for 3 days is not effective against B. gibsoni infection in splenectomized dogs.

Journal Article↗
PubMed1988

Contrasting reflex effects of chemosensitive and mechanosensitive vagal afferents.

Previous studies have identified two distinct types of cardiac vagal afferents, mechanosensitive and chemosensitive. We tested the hypothesis that these two types of vagal afferents mediate different reflex sympathetic nerve responses. We compared effects of stimulation of chemosensitive and mechanosensitive vagal afferents on renal and adrenal sympathetic nerve activity in rats. In anesthetized, sinoaortic baroreceptor-denervated rats, we measured arterial pressure, heart rate, and renal and adrenal sympathetic nerve activity during intrapericardial administration of phenyl diguanide as a stimulus for chemosensitive afferents and during volume expansion and acute occlusion of the ascending aorta as stimuli for mechanosensitive afferents. Stimulation of chemosensitive afferents with phenyl diguanide (3, 10, and 30 micrograms/kg intrapericardially) caused decreases in renal sympathetic nerve activity (-36 +/- 5, -52 +/- 11, and -71 +/- 5%; p less than 0.01) and in arterial pressure and heart rate but increased adrenal sympathetic nerve activity (+14 +/- 27, +63 +/- 21, and +83 +/- 28%; p less than 0.05). These responses were abolished by vagotomy. Intrapericardial injection of saline vehicle did not change renal and adrenal sympathetic nerve activity. In contrast to the effects of phenyl diguanide, activation of mechanosensitive afferents by volume expansion with intravenous infusion of 6% dextran in 0.9% saline (Dextran 75) decreased both renal and adrenal sympathetic nerve activity. Stimulation of mechanosensitive afferents by acute occlusion of the ascending aorta also decreased both renal and adrenal sympathetic nerve activity. These results indicate that chemosensitive and mechanosensitive cardiac vagal afferents produce different reflex responses: Chemosensitive afferents increase and mechanosensitive afferents decrease adrenal sympathetic outflow.

Adrenal Glands↗
PubMed1988

Predicting serum lithium concentration using Bayesian method: a comparison with other methods.

Two pharmacokinetic approaches (single-point Bayesian and two fixed volume of distribution-iterative methods) for predicting serum lithium concentrations in patients treated with lithium carbonate for manic-depressive illness or cyclic neutropenia in Kyushu University Hospital were evaluated and compared retrospectively. Prior to these analyses, three methods (prediction using mean parameters reported by Mason et al., the Pepin method, and the Zetin method) without measuring serum concentrations were also compared. In the Bayesian analysis, the effect of population mean parameters (reported by Mason et al. and Pepin et al.), which were used as initial estimates in a fitting process, on predictive performance was also studied. Forty five patients (21 male, 24 female) were included in this study. The average number of determinations per patient was 6.3, and the sampling times ranged from 2 to 18 h after the last dose. Serum lithium concentrations were measured by atomic absorption spectrometer. The Bayesian method used a computer program (PEDA) developed previously by one of us. The prediction using the population mean values from Mason's report gave the least root mean squared error (RMSE; a composite measure for bias and precision of prediction), and was considered to be the most precise among the methods without measuring serum concentrations. Among the methods using a single measured concentration, the Bayesian prediction was less biased and more precise than that by the two fixed volume of distribution-iterative methods. The Bayesian method reduced prediction error in serum concentration prediction compared with those obtained from population mean parameters in both cases: A high reduction of RMSE was observed when the values from Pepin method were used as initial estimates (from 0.320 to 0.219 meq/l), while, Mason's values gave less reduction (from 0.219 to 0.213 meq/l). In the Bayesian prediction of serum lithium concentration, the selection of population-based initial estimates gave no effect on predictive ability of the Bayesian method in terms of RMSE. In conclusion, the Bayesian method was robust and flexible with regard to dosing schedule, sampling time and number of blood samples, and gave the most clinically acceptable precision among the methods evaluated.

Adolescent↗