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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 667 records · Page 37Linked to original sources
PubMedDate not supplied

In vitro and in vivo release properties of brilliant blue and tumour necrosis factor-alpha (TNF-alpha) from poly(D,L-lactic-co-glycolic acid) multiphase microspheres.

The dissolution properties of two model compounds, brilliant blue and tumour necrosis factor (TNF-alpha), from poly(D,L-lactic-co-glycolic acid) (PLGA) multiphase microspheres were investigated. In addition, the in vivo release of TNF-alpha from the microspheres, in mice, was studied. The microspheres were prepared by an anhydrous multiple emulsion solvent evaporation method. Multiphase microspheres containing brilliant blue exhibited a three phase release profile in vitro, and displayed a significantly lower level of dye released during the initial phase compared to conventional matrix-type microspheres. Slow release of the dye was observed during the second phase, which was followed by a disintegration of the polymer wall during the third phase of the release process. In vitro dissolution profiles of TNF-alpha were calculated by compensation for the simultaneous degradation of the protein in the dissolution medium. The initial burst release of TNF-alpha was significantly reduced with the multiphase microspheres. The three phase release profile, as seen with the dye, was not observed for the microspheres containing the TNF-alpha. The rate of release of the protein from the microspheres was determined in vivo by analysing the residual level of TNF-alpha remaining in the particles following intraperitoneal administration of the microspheres to mice. The release of the protein from the microspheres in vivo was significantly faster than predicted from the results of the in vitro studies. The absence of an initial burst release of TNF-alpha from the multiphase microspheres was reflected in a significant reduction in the plasma level of TNF-alpha when compared to the matrix-type microspheres and a solution of the protein. The controlled release property of the multiphase microspheres is expected to overcome the adverse reactions due to dose dumping that occurs following the local administration of TNF-alpha.

Animals↗
PubMedDate not supplied

Particle size and loading efficiency of poly(D,L-lactic-co-glycolic acid) multiphase microspheres containing water soluble substances prepared by the hydrous and anhydrous solvent evaporation methods.

PLGA multiphase microspheres were prepared by the multiple emulsion solvent evaporation method using acetonitrile as the polymer solvent and mineral oil as the evaporation medium. The preparation process was further developed in the present study to reduce the particle size and to increase the loading capacity of brilliant blue, bovine serum albumin (BSA) and tumour necrosis factor-alpha (TNF-alpha) which were used as water soluble model drug substances. Sorbitan sesqui-oleate (SO-15EX), present at the 1% w/w level in the evaporation medium, prevented agglomeration of the microspheres containing a solid-in-oil (S/O) suspensions as the core phase. This S/O suspension core provided significantly higher loading efficiency of the proteins to the W/O emulsion core. The W/O emulsion system resulted in agglomeration of the protein-loaded microspheres and the loading efficiency decreased significantly. When brilliant blue was included as the model compound, the loading efficiencies were not influenced by the core type. Heavy mineral oil was employed to stabilize the dispersed unhardened microspheres rather than light mineral oil that was reported previously. This anhydrous emulsion system employing the S/O suspension core and containing a dispersion of TNF-alpha enabled the encapsulation of this protein without loss of activity. It was concluded that the anhydrous emulsion system is a suitable approach to prepare multiple microspheres as an alternative to the W/O emulsion system, especially when solvent sensitive proteins are incorporated into the microspheres.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids.

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.

Adult↗
PubMedDate not supplied

Early-stage Alzheimer's disease and multiple subcortical infarction with mild cognitive impairment: neuropsychological comparison using an easily applicable test battery.

We conducted a neuropsychological study comparing early-stage Alzheimer's disease (AD; n = 22) and multiple subcortical infarction with mild cognitive impairment (MSI; n = 22) using an easily applicable test battery which included 8 tests. Two groups were matched for age, education and score on the Mini-Mental State Examination. Patients with AD had significantly lower scores than MSI patients in the delayed recall of the Rey-Osterrieth Complex Figure, while MSI patients had significantly worse scores in the Wisconsin Card-Sorting Test. This suggests that early discrimination of MSI from AD can be made by frontal system impairment in MSI and episodic memory disturbance in the visuospatial domain in AD using simple neuropsychological tests.

Aged↗
PubMedDate not supplied

Ultrastructural and histochemical study of the motor end plates of the intrinsic laryngeal muscles in amyotrophic lateral sclerosis.

Motor end plates of the intrinsic laryngeal muscles in amyotrophic lateral sclerosis (ALS) were examined light and electron microscopically. Light microscopically, typical neurogenic changes such as small angulated fibers and grouped atrophy were found in the intrinsic laryngeal muscles. Acetylcholinesterase (AchE) activities of the neuromuscular junctions (NMJ) of many fibers in ALS were decreased as compared with those of the controls. Some end-plate areas on each fiber detected by AchE histochemistry were larger than those of the controls. Ultrastructurally, muscle fibers in ALS specimens showed several changes; increased number of lipofuscin granules and/or nuclei, numerous mitochondria, and disappearance of the myofilaments. The NMJ also showed various degrees of structural changes. Some NMJ appeared almost normal. Others showed the absence of nerve terminals and Schwann cells covering the former junctional sites. Their primary synaptic clefts were flattened, and the secondary synaptic clefts were relatively well preserved. On occasion, several small nerve terminals were seen on the severely distorted postsynaptic folds, suggesting regenerative findings. In severely degenerated muscle fibers, the NMJ could not be found.

Acetylcholinesterase↗
PubMedDate not supplied

Preparation of multi-phase microspheres of poly(D,L-lactic acid) and poly(D,L-lactic-co-glycolic acid) containing a W/O emulsion by a multiple emulsion solvent evaporation technique.

Multi-phase microspheres of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) containing a water-in-oil (W/O) emulsion were prepared by a multiple emulsion solvent evaporation technique. Acetonitrile was used as the solvent for the polymers and light mineral oil as the dispersion medium for the encapsulation procedure. Process and formulation parameters to optimize the microencapsulation of a W/O emulsion containing water-soluble drugs were investigated. Drug loading efficiencies of 80-100 per cent were obtained under specific preparative conditions. The drug loading efficiency in the microspheres was dependent upon the ratio of the W/O emulsion to polymer and the concentration of surfactant in the mineral oil. Compared to conventional microspheres, in which fine drug particles are homogeneously dispersed in the polymer beads, the multi-phase microspheres permit the higher encapsulation efficiency of water-soluble drugs and eliminate partitioning into the polymer-acetonitrile phase which results in low encapsulation efficiency with conventional solvent evaporation techniques.

Acetonitriles↗
PubMedDate not supplied

Properties of multiphase microspheres of poly(D,L-lactic-co-glycolic acid) prepared by a potentiometric dispersion technique.

Multiphase microspheres of poly(D,L-lactic-co-glycolic acid) (PLGA) were prepared by a multiple emulsion potentiometric dispersion technique. Water-soluble compounds were dissolved in the aqueous phase (W) and emulsified in soybean oil (O) to form a stable emulsion. This primary emulsion was dispersed in a solution of PLGA and acetonitrile (O) to form a W/O/O emulsion. The W/O/O emulsion was then dispersed in a hardening solution of light mineral oil (O) using a potentiometric dispersion technique to produce microspheres of the W/O/O/O type with a very narrow and selective size distribution. The size of the microspheres was controlled by varying the internal diameter of the conductive infusion tube or by the variation of voltage applied to the conductive tube. Particle size analysis revealed a particle size distribution of 1-50 microns for microspheres made by this method as compared to a distribution of 50-500 microns for microspheres made by conventional agitation methods. Chlorpheniramine maleate was encapsulated with a loading efficiency of 88.9% with the potentiometric method as compared with a loading efficiency of 74.3% for the agitation method.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Online support functions of prescription order system and prescription audit in an integrated hospital information system.

The role of the online prescription support functions of a prescription order entry system was analysed and the results of the prescription audit by pharmacists were examined. In the Kochi Medical School Hospital, an online prescription order system has been developed as part of an integrated hospital information system named IMIS (the Integrated Medical Information System), in which all the physicians enter their prescription orders into online display terminals. The prescription order entry system is provided with prescription support functions, which check the entered prescription data, issue warnings, and offer information about drugs or patients. The prescription order system reduces the incidence of simple prescription mistakes and greatly decreases the cases of inquiries by pharmacists. However, results of the analysis show that such functions as warnings of double order and repeated prescription of a drug do not work as well as expected. The system would thus require some kind of intelligence like that of the auditing pharmacists or that of the physicians with accurate knowledge of clinical pharmacology.

Drug Prescriptions↗
PubMedDate not supplied

Ultrastructural study of the remnant liver after extensive hepatectomy in dogs; especially morphological alterations of sinusoidal endothelial cells.

BACKGROUND/AIMS: To investigate the role of sinusoidal endothelial cells in the mechanism of the remnant liver dysfunction after extensive hepatectomy, morphological alteration of sinusoidal endothelial cells and cytoprotective effects of prostaglandin I2 analog were studied by ultrastructural analysis. METHODOLOGY: Mongrel dogs (n = 24) were divided into 3 groups according to the extent of hepatectomy and the use of prostaglandin I2 analog preoperatively. Group 1: 70% hepatectomy (n = 8), Group 2: 84% hepatectomy (n = 8), and Group 3: 84% hepatectomy with administration of prostaglandin I2 analog, preoperatively (n = 8). Morphology of hepatic sinusoidal endothelial cells was examined after hepatectomy in all cases. RESULTS: Group 2: Enlargement of the sinusoidal endothelial fenestrations was transitorily occurred immediately after hepatectomy, but were dramatically decreased in size 24 h after the operation. Most sinusoidal endothelial cells were destroyed and separated from the sinusoidal wall. Fibrin deposits and sludge were found in the Disse's space and sinusoidal lumens, resembling liver failure at 24 h after the operation. Group 1 and 3: sinusoidal endothelial fenestrations remained slightly enlarged at 24 h after the operation, but fibrin deposits or sludge were not observed in sinusoidal lumens. CONCLUSIONS: Our data suggest that extensive hepatectomy changed the morphology of sinusoidal endothelial cells. Administration of prostaglandin I2 analog helped maintain structural integrity of sinusoidal endothelial cells, improved hepatic microcirculation and thus served to reduce remnant liver dysfunction.

Animals↗
PubMedDate not supplied

The remnant liver dysfunction after 84% hepatectomy in dogs.

BACKGROUND/AIMS: We have been investigating the mechanism of remnant liver dysfunction after extensive hepatectomy in a canine model since 1990. This study focused on the role of heat shock protein and hepatocyte apoptosis. METHODOLOGY: Adult mongrel dogs were randomly divided into 3 groups: Group 1, sham operation; Group 2, 70% hepatectomy; and Group 3, 84% hepatectomy. Heat shock protein and hepatocyte apoptosis after hepatectomy were examined by using isolated hepatocytes and Kupffer cells. RESULTS: Heat shock protein significantly increased in Groups 2 and 3, but rose much higher in Group 3. Examination of pure hepatocyte culture showed no apoptosis in Group 2, but significant apoptosis occurred in Group 3. In co-cultures of hepatocytes and Kupffer cells, induction of apoptosis in Group 2 was mild, but it increased earlier and reached very high levels in Group 3. The TNF-alpha level in co-culture supernatant was significantly higher in Group 3 than Group 2. CONCLUSIONS: After extensive (84%) hepatectomy, apoptosis signal transduction predominates over anti-apoptosis signal transduction, despite high expression of heat shock protein in the remnant liver. Accordingly, the cytotoxic mechanism overcomes the cytoprotective mechanism, leading to significant induction of hepatocyte apoptosis and severe liver damage.

Animals↗
PubMedDate not supplied

[A case of progressive supranuclear palsy improved with tandospirone citrate].

We reported a 74-year-old male case of progressive supranuclear palsy (PSP) who responded to tandospirone citrate, a serotonin receptor (5-HT1A) agonist. The patient manifested postural instability and gait disturbance at 71 years. Additionally, he showed vertical gaze paresis, regidity of the neck, extremities and trunk, bradykinesia and mild cognitive impairment. A brain MRI revealed moderate atrophy of bilateral frontal/temporal lobes and of midbrain tegmentum one year after the onset. The patient had been diagnosed as PSP and treated with L-DOPA. However, L-DOPA therapy showed only transient response for a few months. His symptoms deteriorated gradually, and he became unable to sit, stand up or walk by himself. Tandospirone citrate was additionally administered at 30 mg/day. Rigidity and bradykinesia were remarkably improved in two weeks after the start of tandospirone treatment. He became able to stand up and walk a short distance with supports in four weeks. Cognitive disturbance was also slightly improved. Tandospirone citrate was effective on our case of PSP, especially on rigidity. Our findings suggest that combination of levodopa and tandospirone citrate is a useful therapy for PSP.

Aged↗
PubMedDate not supplied

Modulation of multidrug resistance by immunosuppressive agents: cyclosporin analogues, FK506 and mizoribine.

It has recently been reported that an immunosuppressive agent, cyclosporin A, shows a potent overcoming effect on multidrug resistance (MDR). We studied the presence of such a modulating effect of cyclosporin analogues and other immunosuppressive agents, FK506 and mizoribine, in human multidrug-resistant ovarian cancer cells (TAOV/A0.2). The intensity of the overcoming effect of cyclosporin analogues against adriamycin resistance was found to be in the other of cyclosporin D greater than A greater than C greater than H. It was found that cyclosporin D, which has relatively weak immunosuppressive activity, overcame adriamycin resistance in the multidrug-resistant ovarian cancer cells to a remarkable degree. On the other hand, it was found that FK506, a new potent immunosuppressant, could also distinctly modulate adriamycin-resistance. It was found that FK506 conferred chemosensitization upon adriamycin with reincreasing intracellular adriamycin accumulation in MDR cells which was far less than the parent strain. However, in the case of mizoribine, no modulation of drug resistance existed. Such modulation was not necessarily accompanied by immunosuppressive activity and the two functions were thought to be based on different mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Neuronal intranuclear hyaline inclusion disease: report of a case and review of the literature.

A case of neuronal intranuclear hyaline inclusion disease (NIHID) is described. The patient was a 26-year-old man who died of a progressive neurologic disorder, the onset of which occurred at the age of 11 years. Clinically, the disease presented as juvenile parkinsonism, and pathologically it was characterized by multiple-system degeneration in conjunction with the ubiquitous presence of intranuclear hyaline inclusions in neurons of the central and peripheral nervous system including the autonomic ganglia. Smaller and less eosinophilic intranuclear inclusions were also present in a small number of glial cells. The neuronal inclusions emitted a strong yellow-green autofluorescence under ultraviolet light and were composed of filaments 10-15 nm in diameter. The glial inclusions also consisted of similar filaments but their autofluorescence could not be determined with certainty because of their small size and background autofluorescence. A review of the literature revealed 19 similar autopsy cases up to 1987. Since the clinical presentation and distribution of neuronal loss as well as the characteristics of the inclusions showed some differences among the cases, some authors speculated that NIHID represented more than one variant of a multiple-system degenerative disease. However, about half of the reported cases had favorable sites of neurodegeneration, such as the pallidum, substantia nigra, motor nuclei of the brain stem, anterior horn cells, Clarke's column and spinal ganglion as well as similarities among the inclusions. Thus, there seems to be a discrete group among cases of NIHID.

Adult↗
PubMedDate not supplied

Neural mechanism of reading and writing in the Japanese language.

Three Japanese patients presenting with pure alexia showed agraphia for Kanji in addition. A left angular gyrus lesion caused agraphia for both Kanji and Kana, but Kanji reading was preserved. A left posterior inferior temporal (PIT) lesion resulted in alexia and agraphia for Kanji, while the Kana function was preserved. These results imply that the semantic processing of reading Kanji words depends upon the left PIT area, while the phonological reading of Kana is mediated by the left angular gyrus. The PIT area also plays an important role in writing Kanji words.

Aged↗
PubMedDate not supplied

MRI of callosal disconnection due to cerebral infarction.

Magnetic resonance imaging (MRI) was performed to study two cases of callosal disconnection due to cerebral infarction. Both cases had pure alexia and right homonymous hemianopsia. Midsagittal inversion recovery (IR) images demonstrated that the corpus callosum was completely intact, and coronal IR images revealed involvement of the lingual gyrus, fusiform gyrus, forceps major, inferior longitudinal fascicle, and optic radiation in the dominant cerebral hemisphere in both cases. Midline sagittal images provided direct visualization of the corpus callosum but did not provide sufficient information for the study of callosal disconnection syndromes. Coronal reconstructions aided in visualizing the relationship of lesions to the adjacent structures of cerebral white and gray matter. MRI may be one of the most useful tools for understanding the process of interhemispheric transference of information.

Aged↗
PubMedDate not supplied

Beneficial effects of interleukin-2 on natural killer activity in lung cancer patients.

The effects of human interleukin-2 (IL-2) on the growth and natural killer (NK) activities of lymphocytes were evaluated in patients with advanced lung cancer, and compared with age-matched normal subjects. Peripheral blood lymphocytes (PBL) from the patients and the controls were grown exponentially in response to IL-2 and showed no differences in the cell numbers and the proliferative capacities. In both groups, pretreatment for 18 hr with IL-2 was able to augment the NK activity of PBL. Furthermore, PBL propagated in IL-2 over a period of 15 days also demonstrated vigorous NK activity, although there was a relative broad range of NK levels among those from the patient individuals. The present study suggests that the depressed NK activity of PBL from our patients can not be explained by lack of their responsiveness to IL-2, and that human IL-2 can augment the NK activity of PBL and support the growth of PBL-derived cells with high NK levels in patients with lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Direct antitumor effect of cepharanthin and combined effect with adriamycin against Ehrlich ascites tumor in mice.

Direct antitumor effect of cepharanthin (CEP) and the combined effect with adriamycin (ADR), as well as the effect of CEP against body weight loss caused by treatment of ADR were evaluated using ICR mice bearing Ehrlich ascites tumor. Single administration of CEP reduced tumor growth compared to that of the untreated control, but not significantly. However, multiple administration of CEP reduced the tumor growth significantly compared to that of the untreated control (p < 0.001). Simultaneous administration of intratumoral CEP and intravenous ADR reduced the tumor growth significantly compared to that of ADR alone (p < 0.05). Further, CEP restored body weight loss caused by the treatment of ADR (p < 0.01). These findings indicate that the combined administration of CEP and ADR may be effective in cancer treatment.

Alkaloids↗