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Biomedical subjects

I Kaetsu

Publications and source records attributed to I Kaetsu.

At least 19 recordsLinked to original sources

[Prolonged antinociceptive effect after epidural injection of polyethylene glycol-morphine composites in rats].

Epidurally administered morphine is useful in the management of postoperative or cancer pain, and a reliable method which can produce prolongation of analgesia with a single dose may be very useful. We synthesized a polyethylene glycol-morphine (PEG-morphine) composites and examined the duration of analgesia after a single epidural administration dose of this agent in the rat. The molecular weight of PEG was functionally evaluated. PEG-morphine was injected surgically along the epidural space. Morphine in doses of 2.5, 5.0 and 7.5 mg and PEG only were administered. A second group of animals received intramuscular injections of PEG-morphine (5.0mg). Animals were then tested for analgesia using the tail-flick test. The antinociceptive effect of 7.5mg was significantly longer than that of 2.5mg or 5.0mg. Neither PEG alone nor intramuscular administration of PEG-morphine induced antinociceptive effect. Sensory blockade was reversible and the animal appeared to have normal sensory perception. We conclude that the antinociceptive effect of morphine is dose-dependent and its duration can be prolonged when administered as a PEG-morphine composite in the epidural space.

Analgesics, Opioid

Interstitial chemotherapy with biodegradable ACNU pellet for glioblastoma.

For patients with nonresectable glioblastoma (GB) or recurrent GB, we have recently been using an interstitial chemotherapy with biodegradable polylactic acid pellets containing nimustine chloride (ACNU), in combination with superselective arterial ACNU injection, routine irradiation and chemotherapy. The ACNU pellets are prepared by mixing polylactic acid powder and ACNU, and then melting the mixture at low temperature and moulding it into a thin pellet. Pharmacological anticancer activity was experimentally demonstrated by the finding that a region of suppression was present surrounding an ACNU pellet placed in a B6 melanoma cell culture disc, but that no such suppression was present around a control pellet. In order to determine the spatial and temporal distribution of ACNU, a small pellet (ACNU: 0.6 mg) was implanted in the frontal lobe of rats. ACNU concentration determined by HPLC was 61.0 micrograms/g brain tissue on day 1. 22.5 on day 3, and 5.5 on day 7; small amounts of ACNU were in fact released for at least 4 weeks after implantation. This pellet was used for the clinical treatment of 11 GB patients. Four patients had several pieces of pellets implanted immediately after CT-guided stereotactic biopsy, and the other 7 had pellets placed in residual tumor after partial removal at craniotomy. No ACNU was detectable in serum. CT studies obtained at subsequent appropriate intervals disclosed gas formation around the pellets, a slight increase in edema, and necrosis or decrease in CT enhancement of tumor beginning around day 12 after implantation. Bone marrow suppression did not occur, since ACNU was administered interstitially and in the range of 50-200 mg (average: 126 mg) per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

In vivo release of cisplatin from a needle-type copolymer formulation implanted in rat kidney.

Cisplatin, cis-dichlorodiamine platinum (II), was incorporated in a needle-type copolymer formulation (0.8 mm diameter, 6 mm long) by radiation-induced polymerization. The copolymer used was copoly(diethylene glycol dimethacrylate/polyethylene glycol #600 dimethacrylate, 80/20 vol%). This copolymer, containing 6 mg of cisplatin, was implanted into the kidney of adult male Wistar rats (420 +/- 20 g). A total of 70 d was required for 100% release of cisplatin in vivo. The kidney tissue surrounding the formulation was strongly necrotized by the action of cisplatin. Two layers of necrosis could be distinguished: necrotic tissue surrounding the formulation and necrobiotic tissue surrounding the necrotic tissue. The amount of necrotic tissue changed markedly over time, but no change was apparent in the amount of necrobiotic tissue. The maximal amounts of necrotized tissue were observed 14 d after implantation: 3100 microns and 600 microns thick for the necrotic and necrobiotic tissues, respectively.

Animals

Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits.

A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.

Animals

[Treatment of malignant brain tumors with slowly releasing anticancer drug-polymer composites].

The purpose of this study is to present the methodology and results of a clinical trial of local chemotherapy of malignant brain tumors based on slowly-releasing anticancer drug-polymer composites. The slowly releasing drugs were prepared by combining and mutually dispersing anticancer agents with glassified monomers containing 10% polymetacrylic methyl acid and then this compound was frozen at -78 degrees C and exposed to 1 X 10(6) rad of gamma rays from cobalt 60. Thus we prepared a compound of polymers and anticancer agents. We used needle-shaped capsules of this compound. These capsules release the drug very slowly over 40 days. We administered locally to the malignant brain tumors with either slowly releasing mitomycin, slowly releasing adriamycin, slowly releasing ACNU or slowly releasing 5 Fu drugs. The following techniques were employed in implantation these capsules. Implantation into the remaining tumor wall at the time of excision. Implantation into the tumor by CT-guided stereotactic method. We implanted these drugs into tumor of 55 cases, thereafter we conducted both radiation and chemotherapy with ACNU in most patients. This method has the following advantages: It is possible to be employed to different types of anticancer agents. Both dosage and releasing time can be adjusted. It is possible to administer these capsules postoperatively by the stereotactic method. The clinical study consists of 55 patients, 20 cases of anaplastic astrocytoma, 23 cases of glioblastoma multiforme, 5 cases of oligodendroglioma, 3 cases of medulloblastoma and 4 cases of others. Survival rate estimated by Kaplan-Meier method was 47% in glioblastoma at 12 months and 91% in anaplastic astrocytoma at 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents

Preparation by irradiation of a solid support for enzyme immunoassay.

Reagents (immobilized anti-alpha-fetoprotein discs) having a porous structure were prepared for enzyme immunoassay of alpha-fetoprotein by radiation polymerization at low temperatures. Discs were attached to sticks for easy handling. The activity (determined by absorbance at 492 nm) of the discs varied with the hydrophilic properties and size of the disc. The discs are sufficiently sensitive and precise for enzyme immunoassay of alpha-fetoprotein.

Animals

Immobilization of enzymes masks their active site.

We studied the effect of immobilizing cellulase to carboxycellulose sodium by radiation polymerization on the masking of the active site of the enzyme. Masking of the enzyme during the preparation of immobilized enzyme was assayed at low temperature. The activity of immobilized enzyme was retained during repeated batch reactions, indicating that the enzyme was firmly trapped in the polymer matrix. Various compounds (designated monomers) were used to dissolve the carboxymethylcellulose; enzyme activity was affected by the nature of the monomer, by the monomer concentration, and by the solubility of the substrate in monomer.

Binding Sites

Sheets obtained by radiation polymerization for enzyme immunoassay.

Immobilized anti-alpha-fetoprotein sheets, which were attached to sticks, for enzyme immunoassay of alpha-fetoprotein were prepared by radiation polymerization of hydrophilic monomers. The relationship between the preparation conditions and the activity of the sheets was studied. The activity varied with monomer concentration, hydrophilicity of polymer matrix, the amount of coating solution, and antibody concentration. The sheets obtained at relatively low monomer and antibody concentrations appeared to give a high activity. It was found that the sheets are applicable for the enzyme immunoassay of alpha-fetoprotein with high sensitivity.

Humans

Behavior of enzyme activity in immobilized proteases.

Proteases such as trypsin, alpha-chymotrypsin, papain, and thermolysin were immobilized by radiation polymerization of various monomers at low temperatures, and behavior of enzyme activity in immobilized proteases was studied. The enzyme activity in immobilized proteases appeared to be different by the kind of proteases; the order of the magnitude of the enzyme activity was papain greater than trypsin greater than thermolysin greater than alpha-chymotrypsin. This difference of the enzyme activity was explained by the change of the molecular conformation in enzyme reaction.

Chymotrypsin

Polymeric microspheres for immunoresearch.

New microspheres having functional aldehyde groups have been prepared by radiation polymerization of acrolein solution containing hydroxyethyl methacrylate and glutalardehyde. The size distribution in the microspheres was narrow and average particle diameter was 1 - 2 micron. The binding ability of the microspheres to antigen increased by increasing the concentration of glutalardehyde. The preparation procedure of the microspheres is simple. The microspheres can be used for immunoresearch.

Antigens

Flexible porous discs by radiation polymerization method for enzyme immunoassay of alpha-fetoprotein.

New porous discs for enzyme immunoassay of alpha-fetoprotein (AFP) have been prepared by radiation polymerization of various monomers at low temperature. The activity (optical density) of immobilized anti-AFP disc varied with irradiation temperature, anti-AFP concentration, and the hydrophilicity of monomer, in which copolymerization of hydrophilic 2-hydroxyethyl methacrylate and hydrophobic monomers at low temperature below 0 degrees C gave a high activity. The immobilized anti-AFP disc was flexible and had a porous structure. The immobilized anti-AFP discs in dry state are convenient for storage. The minimum serum volume in the assay was 5 microliter. A good correlation (r = 0.98) was noted between AFP concentrations measured by ratio immunoassay and enzyme immunoassay with immobilized anti-AFP disc. The mean recovery of AFP (16-80 ng) added to serum was 95-110%.

Animals

Polyacrolein microspheres as immunoreagents.

Polyacrolein microspheres were prepared by radiation polymerization of acrolein in the absence of emulsifying or stabilizing agent. The microspheres had functional surface aldehyde groups permitting covalent binding with antibody in 1 step. The particle size of the microspheres varied with polymerization conditions, especially irradiation temperature. The microsphere antibody conjugates obtained by binding immunoglobulins to polyacrolein microspheres were used to label cells. The reactivity of microsphere antibody conjugates was shown by specific aggregation by antigen.

Acrolein

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization.

Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity.

Acrylates

Cell culture on polymers prepared by radiation-induced polymerization of various glass-forming monomers.

The growth of cells on polymers prepared by the radiation polymerization of monomethacrylate and dimethacrylate was investigated. Cell growth was affected greatly by such properties of the polymers as water content, wettability, and porosity. Growth was promoted remarkably by rinsing the polymers with warm water at 60-70 degrees C and by irradiation of polymers with an electron beam. Cell growth decreased with increasing oxyethylene length (n) in the polymerized dimethacrylate of same series, CH2C(CH3)CO(OCH2CH2)nOCOC(CH3)CH2. A decrease in the hydrophilicity of the polymer increased cell growth rate. Formation of pore structures in the polymer films also increased the cell growth.

Animals

Cell culture on polymers prepared by radiation-induced grafting of various monomers.

The adhesion and growth of tissue cells on polymers prepared by radiation grafting was investigated. The apparent rates of initial attachment and growth of Chang liver and C6 cells were promoted on surfaces with increased wettability and with a heterogeneous structure for grafted polyvinyl fluoride film. The degree of cell attachment and growth on surfaces having a dense microblock structure, formed by grafting of methyl methacrylate in acetone solvent, was greater than that caused by other factors, such as wettability.

Animals

In vivo release of testosterone from vinyl polymer composites prepared by radiation-induced polymerization.

Polymer-testosterone composites with long periods of controlled slow release were made by radiation-induced polymerization in a supercooled state at low temperature using glass-forming monomers. The in vitro release of testosterone from various vinyl polymer composites was found to follow a matrix-controlled process (Q-t1/2). The rate of drug delivery was accelerated with increasing water content of polymers. In experiments in vivo, the composites were implanted subcutaneously in the back of castrated rats during the 30 day test period. The in vivo release rate of testosterone was a little smaller than in vitro. This difference between two releases also increased with the increase of hydrophilicity of polymer. The physiological response in rats was investigated by measuring the weight of ventral prostate and serum testosterone concentration with testosterone-containing composites. The weight of ventral prostate increased linearly with increasing rate of drug release and the serum testosterone concentration could be correlated with the release and with the weight increase of ventral prostate. It was found from microscopic observation that the used polymer carriers had relatively good biocompatibility to cause little foreign body reaction.

Animals

In vivo release of testosterone from protein--vinyl polymer composites.

Hydrophilic vinyl polymer-protein composites containing testosterone were made by means of thermal denaturation of albumin after radiation-induced polymerization of 2-hydroxyethylmethacrylate (HEMA) at--78 degrees C. The albumin-HEMA mixed polymer can be considerably digested with trypsin. The degree of digestion was smaller than that expected from calculation. It was deduced that the digestion of the albumin component was retarded in the presence of HEMA. The same tendency was observed in in vivo experiments. At the same time, in vivo release of testosterone was depressed in albumin-HEMA mixed polymer composite in accordance with the weight decrease of polymer composite resulting from digestion. The effect of testosterone on the weight of ventral prostate was investigated using composites in castrated Wistar rats. The effect was larger in the controlled slow release from implanted composites rather than that of dosage by injection. The microscopic observation showed that the inflammation and foreign body reaction in rat tissue were retarded in albumin-HEMA mixture polymer composite compared with 100% albumin composite.

Animals