Biomedical subjects

T Hino

Publications and source records attributed to T Hino.

At least 73 records · Page 4Linked to original sources

PubMed1995

Single photon emission computed tomography in systemic lupus erythematosus with psychiatric symptoms.

Single photon emission computed tomography (SPECT) with n-isopropyl-p-[123I]iodoamphetamine (IMP) was performed on 20 patients with systemic lupus erythematosus (SLE). Fifteen of the patients showed areas of hypoperfusion. All nine patients who had florid psychiatric manifestations at the time the SPECT was performed had hypoperfusion areas. Four patients who had abnormal SPECT findings during psychiatric remission had psychiatric exacerbation one to six months after the SPECT. Four patients who had no hypoperfusion during psychiatric remission had good psychiatric prognoses. Two patients who had no history of psychiatric abnormality but showed hypoperfusion had psychiatric manifestations one month after the SPECT. The IMP-SPECT may be useful as a biological marker that represents the activity of cerebral involvement underlying psychiatric manifestations and the presence of subclinical CNS involvement.

Adolescent↗

PubMed1995

Desensitization of vascular tissue to parathyroid hormone and parathyroid hormone-related protein.

Although PTH and PTH-related protein (PTHrP) are vasodilators, prolonged exposure to elevated levels of PTH is often associated with hypertension. We investigated the effects of prolonged incubation with PTH or PTHrP on arterial segments and cultured vascular smooth muscle cells (VSMC). PTH or PTHrP transiently relaxed precontracted arterial segments within 10 min. Additional PTH or PTHrP added after 40-min exposure to these peptides had little effect on vascular tone, whereas forskolin, isoproterenol, isobutylmethyl-xanthine, or acetylcholine were still potent. In fura 2-loaded VSMC, 5-min incubation with PTH or PTHrP attenuated angiotensin II (Ang II)-induced calcium mobilization, an effect that was reduced by preincubation of VSMC with PTH for 1.5 h. Similarly, 1.5-h preincubation with PTH or PTHrP decreased the cAMP response to these peptides but not to forskolin or NaF. Ang II potentiated the cAMP response to PTH and PTHrP but was also subject to desensitization. Nle8, 18Tyr34 bovine PTH(3-34) amide did not desensitize vascular tissue to PTH or PTHrP. Our results suggest that homologous desensitization to PTH or PTHrP in vascular tissue requires receptor stimulation, occurs proximal to G stimulatory protein, and impairs attenuation of calcium mobilization by PTH or PTHrP. This may be a mechanism by which vasodilator effects of these peptides are decreased with prolonged elevation of PTH levels.

Angiotensin II↗

PubMed1995

[Aerosolization of lactide/glycolide copolymer (PLGA) nanospheres for pulmonary delivery of peptide-drugs].

Lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

Administration, Inhalation↗

PubMed1994

In vitro drug release behavior of D,L-lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method.

Nanospheres with D,L-lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion method. Nafarelin acetate (NA), a luteinizing hormone-releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone-dichloromethane-water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200-300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of the rapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water-soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug-release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found tht the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the porous matrix structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Preparation of agglomerated crystals for direct tabletting and microencapsulation by the spherical crystallization technique with a continuous system.

Adhesive and cohesive properties of chlorpromazine hydrochloride (CP) crystals were modified to improve their powder processing, e.g., direct tabletting and microencapsulation, by agglomeration. Moreover, sustained-released gelling microcapsules of CP were devised to prolong the pharmacological effect. The spherical crystallization technique was applied to prepare agglomerates for direct tabletting and microencapsulation to use them as core materials. The ethanolic solution dissolving CP was poured into a stirred cyclohexane, yielding spherically agglomerated crystals. The resultant agglomerates were free-flowing and easily packable spheres with average diameters of 200 to 1000 microns. The agglomerates reserved the high compressibility of the original powder having a small particle size (14 microns). The compression behavior represented by Heckel's equation suggested that the agglomerates were disintegrated to individual primary crystals at low compression pressures, and then they were closely repacked and plastically deformed at higher pressures. After agglomeration, microencapsulation was continuously performed in the same batch by a phase separation method. Coacervate droplets produced by pouring cyclohexane into a dichloromethane solution, dissolving polyvinyl acetate as a coating polymer, were added to the crystallization system under stirring, to prepare the microcapsules. By filling the microcapsules in gelatin hard capsules or tabletting them, their drug release rates became retarded compared with the physical mixture treated in the same way, having the same formulation as the microcapsules. This phenomenon was due to the gelation of polyvinyl acetate of the microcapsules in the dissolution medium, whose glass transition temperature is very low. This novel sustained-release dosage form is termed "gelled microcapsules."

Adhesiveness↗

PubMed1994

Substrate Preference in a Strain of Megasphaera elsdenii, a Ruminal Bacterium, and Its Implications in Propionate Production and Growth Competition.

The NIAH 1102 strain of Megasphaera elsdenii utilized lactate in preference to glucose when the two substrates were present. Even when lactate was supplied to cells fermenting glucose, the cells switched substrate utilization from glucose to lactate and did not utilize glucose until lactate decreased to a low concentration (1 to 2 mM). Since substrate utilization was shifted gradually without intermittence, typical diauxic growth was not seen. The cyclic AMP content did not rise markedly with the shift in substrate utilization, suggesting that this nucleotide is not involved in the regulation of the shift. It was unlikely that propionate was produced from glucose, which was explicable by the fact that lactate racemase activity dropped rapidly with the exhaustion of lactate and cells actively fermenting glucose did not possess this enzyme. A coculture experiment indicated that M. elsdenii NIAH 1102 is overcome by Streptococcus bovis JB1 in the competition for glucose, mainly because M. elsdenii NIAH 1102 is obliged to utilize lactate produced by S. bovis JB1; i.e., glucose utilization by M. elsdenii NIAH 1102 is suppressed by the coexistence of S. bovis JB1.

Journal Article↗

PubMed1994

Parathyroid hormone analogues inhibit calcium mobilization in cultured vascular cells.

Parathyroid hormone and parathyroid hormone-related protein lower blood pressure and relax contracted arteries. Parathyroid hormone also attenuates angiotensin II-induced vasoconstriction. To determine the cellular mechanism or mechanisms by which parathyroid hormone analogues antagonize pressor effects, we examined the effect of these peptides on angiotensin II-induced calcium mobilization in fura 2-AM-loaded cultured rat vascular smooth muscle cells. Either 100 nmol/L parathyroid hormone or parathyroid hormone-related protein significantly reduced the amount of calcium mobilized by 100 nmol/L angiotensin II. The attenuating effect of these peptides was mimicked by 10 mmol/L forskolin and 10 mmol/L isobutylmethylxanthine and was not dependent on the presence of extracellular calcium. This effect of the parathyroid hormone analogues was reduced when cells were pretreated with 100 mmol/L 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. Combined inhibition of cyclic nucleotide-dependent protein kinases eliminated the inhibitory effect of parathyroid hormone, whereas protein kinase C inhibition had no effect. Parathyroid hormone analogues decreased the amount of calcium released by inositol 1,4,5-trisphosphate in digitonin-permeabilized vascular smooth muscle cells. This effect was inhibited by treatment with 2',5'-dideoxyadenosine. These results suggest that these peptides attenuate inositol 1,4,5-trisphosphate-sensitive calcium mobilized by angiotensin II via an adenylate cyclase-dependent mechanism. This may be a mechanism by which acute administration of parathyroid hormone or parathyroid hormone-related peptide antagonizes vasoconstriction.

Animals↗

PubMed1994

Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.

Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.

Analysis of Variance↗

PubMed1994

Hemodynamic changes in the head and neck after ligation of the unilateral carotid arteries: a study using color Doppler imaging.

For evaluation of the hemodynamics of the collateral circulation to the ligated external carotid artery (ECA) region, we measured the blood flow direction and volume in branches of the ECA in patients with unilateral carotid artery ligation before and during digital suppression of the common carotid artery (CCA) on the ligated and nonligated sides with color Doppler imaging and angiography. The main collateral pathway to the ligated ECA region was the ipsilateral occipital artery through Richter's anastomosis from the vertebral artery in the case of unilateral ECA ligation, and was the contralateral carotid artery in the case of unilateral CCA, ECA, and internal carotid artery resection. The superior and inferior labial arteries were important as the collateral pathway from the contralateral ECA.

Blood Flow Velocity↗

PubMed1994

Mucoadhesion of polymer-coated liposomes to rat intestine in vitro.

Multilamellar liposomes consisting of dipalmitoyl phosphatidylcholine (DPPC) and dicetyl phosphate (DCP) in a molar ratio of 8:2 (DPPC:DCP = 8:2) were coated with three different types of polymers: chitosan, polyvinyl alcohol having a long alkyl chain, and poly(acrylic acid) bearing cholesterols. The existence of polymer layers on the liposome surface was confirmed by measuring the zeta potential of the liposomal particles. The mucoadhesive function of the polymer-coated liposomes was evaluated in vitro using rat intestine. A particle counting method using the Coulter counter was adopted to evaluate the adhesive % of liposomes. Chitosan coated liposomes showed the highest adhesive % among the polymer-coated liposomes tested. No adhesive % was observed for the non-coated liposomes. The adhesion of chitosan-coated liposomes to the intestine wall was confirmed by fluorescence microscopy using pyrene loaded liposomes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

Nuclear magnetic resonance study and secondary structure determination of the antibiotic peptide, aibellin.

Aibellin is a 20-residue peptide antibiotic that has been isolated from the fungus Verticimonosporium ellipticum. Sequence-specific assignment of the 1H- and 13C-NMR signals of aibellin in a methanol solution was achieved by using the two-dimensional NMR technique. Furthermore, its secondary structure was characterized by circular dichroism (CD) and NOESY spectra. The observed NOEs, 3JNHC alpha H coupling constants and amide hydrogen-deuterium (H-D) exchange rates show that the peptide consisted of two alpha-helices and a bent structure around a Pro-14 residue.

Amino Acid Sequence↗

PubMed1994

Effect of aibellin, a peptide antibiotic, on propionate production in the rumen of goats.

Aibellin was administered in feed to goats (16 to 18 kg of BW) for 12 d. At 80 mg/d, the molar percentage of propionate in rumen fluid increased significantly in 8 d, and the effect lasted for as long as 10 d after administration ceased. Total VFA concentration, protozoa numbers, and NDF digestibility were not depressed significantly at this dosage but were reduced at 100 mg/d with little further increase in the molar percentage of propionate. Therefore, the optimal dosage of aibellin was 80 mg/d under our experimental conditions. In contrast, monensin (30 mg/d) and gramicidin D (60 mg/d) decreased total VFA concentration and protozoa numbers when supplemented to obtain molar percentages of propionate comparable to 80 mg/d of aibellin. From these results, aibellin may be easier and safer to use than monensin and gramicidin D to modify rumen fermentation.

Animals↗

PubMed1994

Effects of joint distention in shoulder diseases.

From 1982 to 1992 arthrography was performed in 3707 patients with painful shoulders to determine the role of the subscapular bursal obliteration in the pathogenesis of painful, stiff shoulders and to evaluate the effects of distention on the subscapular bursa. Three hundred thirty-nine patients were excluded from the study because of incomplete data, leaving 3368. There were 2391 male and 977 female patients; their average age was 39.2 years (range, 8-86 years). Obliteration was noted in 1156 patients (34.3%), and filling of the bursa was seen in 2212 patients (67.7%). Function was regained in 178 patients (5%) by fluid distention alone, and in 308 (8%) patients by additional forced motion. Thus, 486 shoulders (14%) underwent distention and mobilization successfully. The most effective motion was forced abduction and internal rotation. Four hundred fifteen subjects were evaluated clinically; immediate pain relief after distention and/or bursting of the subscapular bursa was noted in all. There was also a remarkable improvement in the range of motion in all subjects who underwent distention alone, or in combination with forced mobilization.

Adolescent↗

PubMed1993

The relationship between LeY antigen and the therapeutic efficacy of interferon in chronic hepatitis C.

The expression of LeY antigen (Fuc alpha 1-->2Gal beta 1-->4 [Fuc alpha-->3] GlcNAc beta 1-->R), recognized by the monoclonal antibody BM-1, was studied in peripheral blood T-lymphocyte subpopulations in patients with viral hepatitis, and in liver tissue of patients with acute viral hepatitis. The relationship between the expression of LeY antigen on peripheral blood T-lymphocytes and the effects of interferon (IFN) therapy for chronic hepatitis type C were also evaluated. LeY antigen is not markedly expressed in B or T-lymphocytes of healthy individuals. However, it was strongly expressed in CD8 and CD4 T-lymphocytes in patients with viral hepatitis. In the acute phase of acute viral hepatitis, the expression of LeY antigen was more markedly expressed on peripheral CD8 T-lymphocytes than on CD4 T-lymphocytes. In chronic hepatitis type B and type C, it was significantly expressed more often on CD4 T-lymphocytes. In the liver tissues of patients with acute viral hepatitis, LeY antigen was expressed on hepatocytes and infiltrating lymphocytes. IFN therapy for chronic active hepatitis type C proved most effective when LeY antigen was more markedly expressed on the patient's CD4 and CD8 peripheral blood T-lymphocytes before treatment. Further studies are needed to clarify the relationship between the mechanisms of hepatic cell injury and LeY antigen.

Adult↗

PubMed1993

Low-substituted hydroxypropylcellulose as a sustained-drug release matrix base or disintegrant depending on its particle size and loading in formulation.

Tablets of acetaminophen as a model drug were prepared with low-substituted hydroxypropylcellulose (L-HPC) of various particle sizes at various loadings in the formulation. Drug release into an aqueous dissolution medium (pH 1.2) was remarkably sustained from tablets prepared with fine L-HPC (LH41) at loadings of more than 20%. Tablets prepared with less than 20% LH41 or with coarse L-HPCs (LH11, LH21, and LH31) disintegrated in the medium, resulting in rapid release of the drug. The difference in behavior could not be explained in terms of differences in tablet strength, but in swelling and water uptake abilities of the tablet's polymer. Swelling work (swelling force), water penetration speed, and water uptake of LH41 (4.4-microns average particle size) were much smaller than those of coarse L-HPCs. The formation of a continuous gel-like layer on the surface of tablets containing more than 20% LH41 was another factor to sustain the drug release rate.

Acetaminophen↗

PubMed1993

Purification of arginine-sensitive hemagglutinin from Fusobacterium nucleatum and its role in coaggregation.

Hemagglutinin of Fusobacterium nucleatum was extracted from Triton X-100-pronase P-treated cell envelopes, and was purified by affinity chromatography on L-arginine agarose. The hemagglutinin was inactivated by heating at 70 degrees C for 1 min. The activity was inhibited by L-arginine but was not affected by any sugars or by EDTA. The hemagglutinin aggregated 14 out of 17 strains of oral streptococci tested, and the bacterial aggregating activity was also inhibited by L-arginine. The results indicate the dominant role of this hemagglutinin in the adherence of this bacterium both to host cells and to other bacteria.

Arginine↗

PubMed1993

A study of erythrocyte C3b receptors (E-CR1) in patients with acute viral hepatitis.

Erythrocyte C3b receptors (E-CR1) were assayed by ELISA in 16 patients with acute viral hepatitis. In 13 patients with hepatitis type A, type B, or type non-A non-B, the E-CR1 level was significantly lower in the acute phase than in healthy controls, and recovered in the convalescent phase. The E-CR1 levels in 3 patients with non-A, non-B hepatitis remained below the mean level of the healthy controls. These findings suggest that the E-CR1 level fluctuates in acute viral hepatitis, and that it continues to be reduced in some patients with non-A non-B acute hepatitis.

Acute Disease↗

PubMed1993

Presence of lactate dehydrogenase and lactate racemase in Megasphaera elsdenii grown on glucose or lactate.

Activity of D-lactate dehydrogenase (D-LDH) was shown not only in cell extracts from Megasphaera elsdenii grown on DL-lactate, but also in cell extracts from glucose-grown cells, although glucose-grown cells contained approximately half as much D-LDH as DL-lactate-grown cells. This indicates that the D-LDH of M. elsdenii is a constitutive enzyme. However, lactate racemase (LR) activity was present in DL-lactate-grown cells, but was not detected in glucose-grown cells, suggesting that LR is induced by lactate. Acetate, propionate, and butyrate were produced similarly from both D- and L-lactate, indicating that LR can be induced by both D- and L-lactate. These results suggest that the primary reason for the inability of M. elsdenii to produce propionate from glucose is that cells fermenting glucose do not synthesize LR, which is induced by lactate.

Acetates↗