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Biomedical subjects

N Yui

Publications and source records attributed to N Yui.

At least 19 recordsLinked to original sources

[Influence of the radioactive strontium (89Sr) using for nuclear medical radiation therapy upon radioactive draining-water system].

PURPOSE: Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated. METHODS: The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined. RESULTS: The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values. CONCLUSION: It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.

Bone Neoplasms↗

Hyaluronic acid grafted with poly(ethylene glycol) as a novel peptide formulation.

Hyaluronic acids (HA) grafted with poly(ethylene glycol) (PEG) (PEG-g-HA) were synthesized. The materials characterization, enzymatic degradability and peptide (insulin) release from solutions of the copolymers were examined. Distribution of bioactive peptides within the polymer chain is well-known for combinations of PEG and polysaccharides as aqueous polymer two-phase systems. Insulin was preferentially partitioned into the PEG phase in a PEG/HA solution system. Enzymatic degradation of the copolymers was strongly dependent on the PEG content. Thermal analysis revealed that PEG-g-HA exhibited a variation in phase-separated structures depending on the PEG content. The solution of PEG-g-HA enabled insulin to remain in the PEG moieties dispersed in the HA matrix. Leakage of insulin from the copolymers was dependent upon the PEG content. Leakage rate of insulin from copolymer containing between 7 and 39% by weight of PEG were similar. A dramatic increase in leakage rate occurred when the PEG content was increased to greater than 39% by weight. It is considered that the loaded insulin was partitioned into the PEG moieties and became entangled with the PEG chains. The conformational change of insulin was effectively prevented in PEG-g-HA solutions, although insulin was denatured in storage of both phosphate buffered solution and HA solution. Such a heterogeneous-structured polymeric solution may be advantageous as an injectable therapeutic formulation for ophthalmic or arthritis treatment.

Biodegradation, Environmental↗

Synthesis of theophylline-polyrotaxane conjugates and their drug release via supramolecular dissociation.

Theophylline-polyrotaxane conjugates were synthesized by coupling theophylline with alpha-cyclodextrins (alpha-CDs) in the polyrotaxane. The polyrotaxane is a molecular assembly in which many alpha-CDs are threaded onto a poly(ethylene glycol) (PEG) chain capped with L-phenylalanine (L-Phe). Theophylline-7-acetic acid was activated by coupling with 4-nitrophenol, and then ethylenediamine was allowed to react with the active ester in order to obtain N-aminoethyl-theophylline-7-acetoamide. This derivative was coupled with a 4-nitrophenyl chloroformate-activated polyrotaxane to obtain the theophylline-polyrotaxane conjugates. The conjugates formed a specific association under physiological conditions, depending upon interactions between the theophylline molecules and/or the terminal l-Phe moiety in the conjugates. In vitro degradation of the conjugates revealed that theophylline-immobilized alpha-CDs were completely released by hydrolysis of the terminal peptide linkage in the polyrotaxane. This result indicates that the association of the conjugates does not induce the steric hindrance but rather enhances the accessibility of enzymes to the terminal peptide linkages. It is suggested that our designed drug-polyrotaxane conjugates can release the drugs via the dissociation of the supramolecular structure without steric hindrance of enzymatic accessibility to the terminal peptide linkages.

Bronchodilator Agents↗

67Ga planar imaging with a low-energy collimator and scatter correction using the triple energy window method.

To improve the spatial resolution and contrast of 67Ga planar imaging, we used a low-energy collimator and two lower-energy windows with a triple-energy-window (TEW) scatter compensation method. The spatial resolution is better than with a medium-energy collimator, and the TEW method can correct for scattered photons and reduce the background counts. In a phantom study and a clinical study involving 44 patients, the images obtained by the proposed method were compared with the images obtained with a medium-energy collimator and three energy windows without scatter compensation (the conventional method). The spatial resolution and the counts were measured. Two nuclear medicine physicians interpreted the images and clinical usefulness was evaluated. The spatial resolution and contrast were improved by our proposed method. It enabled the detection of lesions in five locations in the clinical study. The counts were reduced but misreadings were not seen. We conclude that our proposed method shows a clinical advantage over the conventional method. It can be used easily and quickly with commercially available equipment and is useful in clinical practice.

Adult↗

Pulsatile peptide release from multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted and ungrafted dextrans.

Multi-layered hydrogel formulations consisting of poly(ethylene glycol)-grafted dextran (PEG-g-Dex) and ungrafted Dex were investigated as a model of pulsatile drug release. In these formulations, it is considered that the grafted PEG domains act as a drug reservoir dispersed in the Dex matrix based on aqueous polymer two-phase systems. The formulations exhibited surface-controlled degradation by dextranase, and insulin release was observed in a pulsatile manner because of the multi-layered structure: PEG-g-Dex hydrogel layers containing insulin and insulin-free Dex hydrogel layers. Thus, it is suggested that the multi-layered hydrogel formulations using PEG-g-Dex and Dex are feasible for chronopharmacological drug delivery systems.

Animals↗

Effect of acetylation of biodegradable polyrotaxanes on its supramolecular dissociation via terminal ester hydrolysis.

Acetylation of biodegradable polyrotaxanes was examined to estimate the effect on its supramolecular dissociation via terminal ester hydrolysis. The biodegradable polyrotaxanes, in which many alpha-cyclodextrins (alpha-CD) are threaded onto a poly(ethylene glycol) chain capped with L-phenylalanine via ester linkages, were acetylated using acetic anhydride; alpha-CD release behavior was then characterized by in vitro hydrolysis. The degree of acetylation was changed by the concentration of acetic anhydride and the reaction time. The results of the in vitro hydrolysis indicate that the critical degree of acetylation to prolong supramolecular dissociation lies at around 30%. The terminal hydrolysis proceeded completely even with 100% of acetylation. These findings suggest that the hydrophobization of alpha-CDs in the polyrotaxane makes it possible to delay the time to complete the supramolecular dissociation. The hydrophobization of the polyrotaxane is of great importance for designing implantable materials that maintain their supramolecular structure until tissue regeneration with complete terminal hydrolysis.

Acetic Anhydrides↗

Polyrotaxanes: synthesis, structure, and potential in drug delivery.

This article reviews the potential of polyrotaxanes in drug delivery with the historical background of polyrotaxane syntheses. Pseudopolyrotaxanes and polyrotaxanes, including classifications, synthetic methods, structures and physical properties are discussed in the first section. The second section provides our concept of drug carriers using drug-polyrotaxane conjugates in comparison with conventional drug-polymer conjugates. The third and fourth sections describe the synthetic method for biodegradable polyrotaxanes, the conjugation with drugs, and their association under physiological conditions. The fifth section discusses other possibilities for the polyrotaxanes such as drug penetration enhancers. These studies suggest the potential of polyrotaxanes in pharmaceutical applications.

Animals↗

[Tumor imaging using 201Tl chloride and 67Ga citrate in nucleomedical surveys].

Among nucleomedical examinations for cancer, tumor imaging using 201Tl chloride and 67Ga citrate can be easily performed at almost any hospital. However, the planar images usually obtained are not sufficient to detect small tumorous lesions. For more accurate detection, tomographic images particularly single photon emission CT (SPECT) is necessary. SPECT is also indispensable in cancer diagnosis. Whether 201Tl SPECT or 67Ga SPECT is chosen depends upon tumor localization, histological type, and the final purpose of the study. 201Tl accumulates in almost all tumors, but it is not suitable for detection of abdominal lesions, because there is much physiological accumulation in the small intestine and kidney. In contrast, 67Ga does not always accumulate in adenocarcinomas. 201Tl SPECT and 67Ga SPECT are more useful in the functional imaging of cancer than is morphological tumor diagnosis. Both methods are useful in monitoring treatment effectiveness, detecting recurrent lesions after surgery and radiotherapy, and predicting the grade of malignancy of the tumor. Tumor SPECT using 201Tl chloride and/or 67Ga citrate provides clinically useful information not obtained by morphological tumor diagnosis only.

Citrates↗

Dual-stimuli-responsive drug release from interpenetrating polymer network-structured hydrogels of gelatin and dextran.

Interpenetrating polymer network (IPN)-structured hydrogels of gelatin (Gtn) and dextran (Dex) were prepared with lipid microspheres (LMs) as a drug microreservoir, and LM release from these hydrogels was examined in relation to their dual-stimuli-responsive degradation. A phase morphology in the IPN-structured hydrogels was varied with the preparation temperature, i.e. above or below the sol-gel transition temperature (Ttrans) of Gtn. The IPN-structured hydrogel prepared below Ttrans exhibited a specific degradation-controlled LM release behavior: LM release from the hydrogel in the presence of either alpha-chymotrypsin or dextranase alone was completely hindered, whereas LM release was observed in the presence of both enzymes. It is concluded that dual-stimuli-responsive drug release can be achieved by specific degradation of a particular IPN-structured hydrogel.

Delayed-Action Preparations↗

Regulation of intracellular metabolism by biodegradable polyrotaxanes.

Cellular response to our designed biodegradable polyrotaxanes was investigated in terms of changes in cytoplasmic calcium levels in platelets. The polyrotaxanes regulated thrombin-induced calcium increase in platelets although constituent molecules of the polyrotaxanes showed fewer effects on the intracellular metabolism. Further, an increase in membrane fluidity of red blood cell ghosts was significantly observed by the addition of the polyrotaxanes. Static light scattering study revealed that the polyrotaxanes formed a supramolecular association state in relation to the molecular weight of PEG: a loosely packed association with a specific molecular shape. From these characteristics, it is suggested that supramolecular level interactions between the polyrotaxanes and cell membranes regulate the intracellular metabolism. It is concluded that these biodegradable polyrotaxanes can be feasible as temporarily-controlled bioactivator.

Animals↗

Mechanistic aspects of blood-contacting properties of polypropylene surfaces--from the viewpoint of macromolecular entanglement and hydrophobic interaction via water molecules.

Polypropylene surfaces with a particular crystalline-amorphous microstructure have been demonstrated to reduce protein adsorption and platelet activation. Such blood-contacting properties may be affected by the crystalline-amorphous microstructure of the surfaces, although wettability such as dynamic contact angles and surface free energy components were almost constant, being independent from the variation in the microstructure. In order to clarify the mechanistic aspects on their blood-contacting properties, the physicochemical properties of the surfaces were evaluated for a series of compression-molded polypropylene sheets in terms of the work of adhesion and the structure of sorbed water. The work of adhesion of the compression-molded sheets increased with decreasing surface layer crystallinity, presumably due to macromolecular entanglement with a polymeric glue used. The work of adhesion involving macromolecular entanglement may occur between proteins and the surfaces. Thus, a decrease in the surface layer crystallinity is considered to cause an increase in the protein adsorption. The structure of water sorbed into the sheets changed--it was more gaseous (isolated) at the surfaces with a higher crystallinity. This suggests that the hydrophobic interaction via water molecules increased with surface layer crystallinity, resulting in increasing protein adsorption and denaturation. Thus, it is considered that both macromolecular entanglement and hydrophobic interaction are important on the mechanistic aspects of blood-contacting properties of polypropylene surfaces. In order to confirm this hypothesis, the evaluation of the physicochemical properties and blood-contacting properties was also performed on a series of uniaxially drawn polypropylene films. A decrease in the work of adhesion and the hydrophobic interaction at the surfaces was observed with increasing draw ratio, and the protein adsorption and platelet activation were effectively prevented with increasing draw ratio. This result supports our hypothesis. Therefore, it is concluded that the excellent blood-contacting properties of polypropylene surfaces can be achieved by reducing the macromolecular entanglement and the hydrophobic interaction with proteins.

Adhesiveness↗

Venous response after lidocaine administration in arm veins.

We previously reported that cubital venous pressure (Pv) tended to increase initially, but this was followed by a drop in a dose-dependent response after intravenous lidocaine administration in subjects with various diseases. In this study we examined whether Pv responses after small-dose intravenous lidocaine administrations are related to the stimulating effect of lidocaine on vascular smooth muscle (VSM). In 5 subjects free of cardiovascular disease, Pv increased slightly with decreased pulsations after a 10 mg dose (p<0.01) with no change in central venous pressure. In the cinephlebographic test performed on 2 healthy volunteers, Pv increased during recovery from proximal venoconstriction caused by an injection of contrast medium mixed with 10 mg lidocaine. In 9 subjects with cardiovascular disease, deltaPv spread in the same directions (+ or -) after 5 and 10 mg drug administrations. In 6 of those tested with both drug doses, deltaPv had positive means and no significant difference was observed. Thus, Pv responses after small-dose lidocaine administrations are consistent with neither the stimulating effect of lidocaine nor with a dose-dependent response. They could be attributed to the spasmolytic effect of lidocaine on the basal tone of VSM, which could be modulated by disease conditions.

Adult↗

[Frameless registration for chest SPECT and X-ray CT image by volume matching].

Image registration of functional (SPECT) and morphological (X-ray CT/MRI) images has been studied in order to improve the accuracy and the quality of the image diagnosis. This paper describes a new registration method for chest SPECT and X-ray CT images. Presented method is a frameless and automatic registration method which calculates a transformation matrix between two coordinate systems of image data by an optimization method. This registration method uses similar physical characteristics of X-ray CT and transmission CT image. The three-dimensional overlap of the body region is used for image matching. Precision evaluation and visual image evaluation were conducted. The result of the precision evaluation with a phantom and clinical data suggested the clinically acceptable robustness in registration procedure. Visual evaluation of registered images confirmed the usefulness of this method in clinical applications.

Algorithms↗

Reduction of surface-induced platelet activation on phospholipid polymer.

omega-Methacryloyloxyalkyl phosphorylcholine (MA-PC) polymers which have been synthesized with attention to the surface structure of a biomembrane show excellent blood compatibility, i.e., resistance to protein adsorption and blood cell adhesion. To clarify the stability of platelets in contact with the MAPC polymer surfaces, cytoplasmic free calcium concentration ([Ca2+],) in the platelets was measured. A platelet suspension was passed through a column packed with various polymer beads after treatment with plasma, and the [Ca2+]i in the platelets eluted from the column was measured. The [Ca2+]i in contact with the MAPC polymers, i.e., poly[2-methacryloyloxyethyl phosphorylcholine-co-nbutyl methacrylate (BMA)] (PMEB) and poly(6-methacryloyloxyhexyl phosphorylcholine-co-BMA) (PMHB), was less than that in contact with poly(BMA). However, poly(10-methacryloyloxydecyl phosphorylcholine-co-BMA) (PMDB) was not effective in suppressing the increase in [Ca2+]i, and thus was at the same level as in the poly(BMA). This result indicated that platelets in contact with PMEB or PMHB were less activated compared with those in contact with PMDB and poly(BMA). Moreover, the state of the platelets adhered to these polymer surfaces, both morphologically and immunologically, was examined. Scanning electron microscopic observation of the polymer surface after contact with a platelet suspension revealed that many platelets adhered and changed their shape on the poly(BMA). The numbers of adhetent platelets were reduced on all MAPC polymer surface. The relative amount of alpha-granule membrane glycoprotein (GMP-140) which appears on the cell membrane by activation of platelets on the PMEB surfaces was less than that on poly(BMA) and poly(2-hydroxyethyl methacrylate). These results suggest that PMEB and PMHB suppressed not only platelet adhesion but also activation of the platelets in contact with these surface.

Animals↗

Thallium-201 single-photon emission tomography in the treatment follow-up of nasopharyngeal carcinoma.

In order to assess the usefulness of thallium-201 single-photon emission tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a total of 75 201T1 SPET studies were performed in 18 patients with histologically proven NPC. The findings were compared with those of magnetic resonance imaging (MRI) before and after therapy. Four patients received radiotherapy alone while the other 14 received concurrent chemo-radiotherapy. Treatment response was classified as complete (CR) or partial (PR) based on the findings of MRI and 201T1 SPET. Intense 201T1 uptake by the tumour was seen in all 18 patients before treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201T1 SPET showed 13 CRs and five PRs. In 12 patients, the results of 201T1 SPET were in agreement with those of MRI. In six patients MRI showed PR but 201T1 showed CR. Follow-up (mean 10.6 months) MRI and 201T1 SPET studies of these six patients revealed that tumour gradually decreased and finally vanished in three patients. This preliminary study indicates that 201T1 SPET has potential in the assessment of early response to treatment of patients with NPC when compared with MRI.

Carcinoma↗

Quantitative evaluation in tumor SPECT and the effect of tumor size: fundamental study with phantom.

An experimental study with phantoms was performed in order to evaluate the effect of the tumor volume on the quantitative estimation in tumor SPECT. The ratio of mean count/pixel in the phantom to that of the background (T/N ratio) was well correlated with the size of the phantom: even when the concentration of the Tc-99m O-4 solution of globular phantoms with diameters of 29, 37 and 46 mm was constant, the greater the size of the phantom, the higher was the T/N ratio. This study showed that we should understand that the T/N ratio was certainly affected by the reduction of the tumor size itself whenever we evaluate treatment-response or assess tumor viability after treatment by reference to the T/N ratio.

Evaluation Studies as Topic↗

Abnormal cerebral perfusion in chronic methamphetamine abusers: a study using 99MTc-HMPAO and SPECT.

1. Cerebral blood flow of nine methamphetamine abusers with technetium-99m-hexamethylpropyleneamine oxime (HMPAO) and single photon emission computed tomography (SPECT) as well as morphological examination with magnetic resonance imaging (MRI) were investigated. 2. Six of these subjects exhibited multiple focal perfusion deficits in cerebral cortices without abnormalities in MRI including cerebral atrophy and/or infarctions. 3. Cerebral perfusion deficits were detected in methamphetamine abusers even after a long abstinence period, suggesting that vascular changes were irreversible to some degree. 4. HMPAO SPECT study appeared to be sensitive to the detection of cerebral perfusion abnormalities in drug abusers.

Adolescent↗

Blood compatibility of polypropylene surfaces in relation to the crystalline-amorphous microstructure.

Blood-contacting properties of polypropylene surfaces with different crystalline states at the surface layer were examined in terms of plasma protein adsorption and changes in cytoplasmic free Ca2+ levels in platelets. Though the wettability of polypropylene surfaces was almost constantly independent from the surface layer crystallinity and interlamellar spacing, an increase in adhesiveness was observed with decreasing surface layer crystallinity and interlamellar spacing. It is suggested that the surface properties of the sheets varied in relation to the crystalline-amorphous microstructure. Minimum magnitudes in albumin and fibrinogen adsorption were observed on the polypropylene surface with a particular surface layer crystallinity (c. 55 wt%). A decrease in interlamellar spacing resulted in enhancing albumin adsorption and diminishing fibrinogen adsorption. Transient phenomena in plasma protein adsorption were observed on their surfaces with a plasma concentration. It is considered that the polypropylene surface with a particular crystalline-amorphous microstructure reduces the denaturation of adsorbed proteins. An increase in cytoplasmic free Ca2+ levels in platelets was prevented at the polypropylene surface with a surface layer crystallinity of 55 wt%: the particular crystalline-amorphous microstructure of such apolar surfaces as polypropylenes acts to reduce platelet activation. Thus, it is concluded that the blood compatibility of polypropylene surfaces is greatly improved by controlling a crystalline-amorphous microstructure at the surface layer.

Adhesiveness↗