Search PubMed⌕ Search

Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 343 records · Page 19Linked to original sources

Evaluation of new pasty-type implantable devices consisting of poly(epsilon-caprolactone/delta-valerolactone) and Estracyt or estramustine.

Biodegradable pasty-type copolyesters with a relatively low molecular weight of 4500 were synthesized by direct copolycondensation of epsilon-caprolactone (CL) and delta-valerolactone (VL) in the absence of catalysts to evaluate in vivo capabilities of the polymer for implantable controlled release devices in drug delivery systems. The devices in cylindrical shape were prepared by the melt-pressing technique using pasty-type copoly(CL/VL) with 53 mol% CL unit, in which Estracyt and estramustine were used as a water soluble and insoluble drug, respectively. The degradation and drug release in vivo of the devices were examined by subcutaneous implantation in the backs of male rats. The degradation of the device was remarkably accelerated by the presence of hydrophilic Estracyt, and was slightly suppressed by hydrohobic estramustine. The estramustine release profile roughly corresponded to the polymer degradation one. It was found that the degradation of the polymer in the device was affected by hydrophilicity of the drug. A reasonable release of estramustine from the device was kept for a period of more than 20 weeks. Furthermore, the release of the drugs in vivo was able to lead to an atrophy of accessory sex organs such as ventral prostates (VP) and right-side seminal vesicle (SV), resulting in pharmacological influence.

Animals↗

Synthesis, resolution, and renal vasodilation activity of novel DA1 agonists: 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives.

7,8-Dihydroxy-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline (1) and 4-(3,4-dihydroxyphenyl)-7-hydroxy-8-methyl-1,2,3, 4-tetrahydroisoquinoline (2) are potent renal vasodilators which selectively stimulate DA1 (peripheral dopamine receptor-1) receptors. Especially, (S)-(-)-1 is the most potent. Its DA1 agonist activity is about 10 times stronger than dopamine for increasing renal blood flow in anesthetized dogs. The renal and cardiovascular effects of (S)-(-)-1 may be suitable for the treatment of patients with renal insufficiency, heart failure and hypertension.

Animals↗

[Studies on cardiac ingredients of plants. VIII. Preparation of nitrates of proscillaridin and their pharmacological activities].

To reduce the vascular contracting effect of the cardiac glycoside, proscillaridin (1), all kinds of its nitrates were prepared by utilizing effectively an isopropylidene function as a protective group. The pharmacological activities of proscillaridin nitrates were evaluated by the use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase preparations from the dog kidney. Furthermore, the effect for smooth muscle using the helical strips isolated from 13-week old spontaneously hypertensive rat was examined. The positive inotropic effects and Na+, K(+)-adenosine triphosphatase inhibition activities of mononitrates (6, 9, 15) and dinitrates (3, 4, 5) were a little less potent than 1, but those of trinitrate (2) were much reduced. Every nitrate did not exhibited a vascular contracting effect but a relaxing effect. Among them, the vascular relaxing effects of 2',3'-dinitrate (3) and 2',4'-dinitrate (4) were more potent than those of the other nitrates.

Animals↗

Analysis of common epitopes on gag proteins of HIV-1, HIV-2 and SIV[AGM] using monoclonal antibodies against HIV-1.

Five monoclonal antibodies (MoAbs) to gag proteins of HIV-1 were prepared in mice. Western blot analyses showed that three clones recognized p24 and the other two p17. Among the three MoAbs recognizing p24, all recognized two of three strains of HIV-2. The spectra of reactions to SIV[AGM] of these MoAbs against p24 were different from one to another; K3-24 recognized all four strains of SIV[AGM], L6-24 three of them, and K5-24 none of them. Of the two MoAbs recognizing p17, K7-17 recognized two of the three strains of HIV-2 but not any SIV[AGM] strain, and the other clone, L14-17 recognized none of analogous proteins of HIV-2 nor of SIV[AGM]. These results demonstrate that the gag proteins of HIV-2 and SIV[AGM] share some common epitopes with those of HIV-1 which are heterogenic in some degree among the different isolates.

Animals↗

Inhibition of prolyl endopeptidase by synthetic peptide fragments of human beta-casein.

It has been suggested that peptide inhibitors of prolyl endopeptidase (PEP) may act as anti-amnestic agents. In the hope of finding PEP inhibitors in milk proteins, we synthesized a total of 37 human beta-casein peptide fragments containing proline residues. It was found that the peptides with PEP inhibition activity in vitro were located in the region of amino acid residues 49-59 of human beta-casein. The most potent inhibitor was Ile-Tyr-Pro-Phe-Val-Glu-Pro-Ile (IC50 = 8 microM).

Amino Acid Sequence↗

[Diagnosis of paternity by deduction of the probable genotype of the deceased person from the relatives--in addition to the examination of the Essen-Möller value and diagnosis of paternity based on the probability distribution of log (Y/X)].

1) The present paper deals with the general formulas of paternity probability, applicable to any cases where the putative man and/or the plaintive mother are deceased, using the blood types of various relatives. Two typical examples are described. 2) Bayes's theorem is applied to the calculation of probability of paternity using the Essen-Möller's formula, in which a putative father is to be compared with any one of the men in the general population whose blood types are unidentified. Statistically, those men are supposed to have any one of several blood types, depending on the frequency of occurrence of those types. This means that their blood types include the blood type of the putative father. According to Bayes's theorem, however, probability calculations are valid only when the two types to be compared are mutually exclusive. Consequently, the theorem should not be applied to probability calculations using the Essen-Möller's formula. 3) A new basis of judgement for the diagnosis of paternity is proposed using the probability distribution of the relative frequencies of log (Y/X) for true father and that for non-father.

Blood Group Antigens↗

Thermo-responsive hydrogels based on acryloyl-L-proline methyl ester and their use as long-acting testosterone delivery systems.

New thermo-responsive hydrogels were synthesized by copolymerizing acryloyl-L-proline methyl ester (A-ProOMe) with minor amounts of 2-hydroxypropyl methacrylate (HPMA) or polyethylene glycol 600 dimethacrylate (14G), using gamma-rays from a 60Co source. In water, extensive swelling of the hydrogels occurred at 10 degrees C, but there was marked deswelling as the temperature was raised to 37 degrees C. The poly(A-ProOMe-co-HPMA) hydrogel was characterized by an initial rapid shrinkage at the surface in the deswollen state; this shrinkage arose because of the formation of a rigid membrane barrier devoid of micropores. The system is therefore 'surface regulated'. In contrast, no such a barrier formed in the deswollen poly(A-ProOMe-co-14G) hydrogel. The whole matrix shrunk without the disappearance of micropores, and it is therefore a 'matrix pumping' system. Testosterone was incorporated into both these types of hydrogels, and the drug-loaded hydrogels were implanted subcutaneously into the backs of castrated rats. The daily dose of testosterone released in vivo from the poly(A-ProOMe-co-HPMA) hydrogel was constant at approximately 30 micrograms/day throughout an experimental period of 54 weeks. In contrast, drug release from the poly(A-ProOME-co-14G) hydrogel reached a maximum after one week and then decreased linearly with time down to the 7th week, when it was undetectable. These conclusions were supported by the changes in weight of the ventral prostates and right-side seminal vesicles of the rats, which were restored to normal when delivery of the testosterone was sustained.

Animals↗

[A case report of anesthetic management of orthotopic liver transplantation from a living donor to his son].

In November 1989, transplantation of a liver graft from a living related donor was performed at Shimane Medical University Hospital. The donor was a 26-year-old man and the recipient his 1-year-old son. The child had been in end stage of liver cirrhosis. Before the surgery, he required intensive care because of massive bleeding from varices. Anesthesia of the recipient was rapidly induced with ketamine and the trachea was intubated with succinylcholine using cricoid pressure. Anesthesia was maintained with enflurane, fentanyl and pancuronium. Nitrous oxide was used only in the preanhepatic period. Total surgical time and anesthetic time were 945 min and 1065 min, respectively. Total estimated blood loss was 3650 ml and 2780 ml of fresh whole blood was transfused. Careful attention was paid to body temperature, serum potassium, ionized calcium and blood coagulation function, as well as to general cardiovascular and respiratory functions. During anhepatic period, the inferior caval vein was not clamped. Hemodynamic function was relatively stable throughout the operation. At the time of reperfusion of the transplanted graft, there was little change in serum potassium levels or other parameters. Postoperative mechanical ventilation was required for 8 days.

Adult↗

Lymphangioma of the jejunum: report of a case.

We report a very rare case of jejunal lymphangioma. A 16-year-old male sustained injuries to abdominal internal organs in a traffic accident. During emergency operation, a cystic tumor was incidentally detected in the jejunum and adjoining mesenterium and treated by segmental resection of the jejunum. The cystic tumor (5.0 x 7.0 cm) was multilocular and demonstrated to be a cavernous lymphangioma by histopathological examination. The pathology, diagnosis, and treatment of this disease described in the literature are reported.

Adolescent↗

Effects of indomethacin and prostaglandin E2 on amylase secretion by rat parotid tissue.

Indomethacin increased the secretion by low concentrations of isoproterenol (IPR, 30-100 nM) and decreased the secretion by a high concentration of IPR (1 microM). Indomethacin also had opposite effects on the secretions induced by low and high concentrations of norepinephrine (NE). PGE2 did not affect the secretions induced by IPR and NE, but it reversed the stimulatory and inhibitory effects of indomethacin. These findings suggest that PG has a role in modulating the amylase secretory response of the rat parotid gland.

Amylases↗

Localization of sulfated glucuronyl glycolipids in human dorsal root and sympathetic ganglia.

Sulfated glucuronyl glycolipids (SGGLs) in human dorsal root ganglion (DRG) and sympathetic ganglion (SG) were analyzed biochemically and immunohistochemically. SGGLs were enriched in human DRG (1.02 +/- 0.23 micrograms/mg protein), whereas much lower concentrations of these glycolipids (0.043 +/- 0.23 micrograms/mg protein) were detected in SG. Myelin within DRG and SG was immunostained by anti-SGGL antiserum, although only a few myelinated fibers were seen in SG. Nerve cell bodies or unmyelinated fibers were not immunostained. Subcellular fractionation study of human DRG demonstrated that these glycolipids were not only enriched in myelin but also in the axolemma-enriched fraction. These data are consistent with the view that SGGLs may be expressed on myelinated fibers in myelin and axolemma, suggesting that these compounds may play an important role in regulating myelinogenesis.

Chromatography, High Pressure Liquid↗

In vitro and in vivo hematopoietic effect of mutant human granulocyte colony-stimulating factor.

About 100 derivatives of human recombinant granulocyte colony-stimulating factor (rhG-CSF) were created by various gene-mutagenic techniques, and KW-2228, in which amino acids were replaced at five positions of N-terminal region of intact rhG-CSF, was picked up and evaluated for its biologic and physicochemical properties in comparison with intact rhG-CSF. KW-2228 showed two to four times higher specific activity than that of intact rhG-CSF in mouse and/or human bone marrow progenitor cells by colony-forming unit assay in soft agar, and by cell-proliferation assay in liquid culture. KW-2228 showed a potency to increase peripheral neutrophil counts when it was administered to normal C3H/He mice by single intravenous injection. Increase of total leukocyte count and neutrophils was observed, with peak level at 8 to 12 hours at low doses (0.5 to 1.0 micrograms/mouse), and the highest level was maintained for 24 to 30 hours at high doses (5 to 10 micrograms/mouse). The granulopoietic effect of KW-2228 was examined by several doses of single course (once daily for 10 days) or multiple courses (twice daily injection for 5 days followed by cessation for 9 days on one cycle, 3 cycles in total) of treatment. KW-2228 showed higher activity than that of rhG-CSF, especially at sub-optimal doses of multiple courses of treatment. Furthermore, KW-2228 was found to be more stable physicochemically and biologically than intact rhG-CSF, especially under thermal conditions at 56 degrees C and in the human plasma at 37 degrees C, suggesting a protease resistancy. Pharmacokinetic study showed that plasma concentration of KW-2228 assayed for its bioactivity maintained a higher level than that of intact rhG-CSF for 60 minutes after intravenous injection of this protein to normal mice. Those results suggest that KW-2228 might show a superior in vivo hematopoietic effect to intact rhG-CSF due to its high specific activity to progenitor cells, and also due to its improved physicochemical, biologic, and pharmacokinetic stability in host animals.

Animals↗

Sequential polydepsipeptides as biodegradable carriers for drug delivery systems.

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).

Amino Acid Sequence↗

Determination of diquat in biological materials by electron spin resonance spectroscopy.

An electron spin resonance (ESR) method already in use for the quantitative analysis of paraquat was applied to the analysis of diquat in blood, serum, urine, tissue homogenates and several drinks without purification of the samples. The diquat radical produced with ascorbic acid at alkaline pH was much more stable than that produced with the commonly used sodium dithionite. Radical decay in solutions covered with n-hexane was less than 5% after 60 min over a wide range of ascorbic acid concentrations. In 0.2 N NaOH solution 85% of the radicals was present even after 24 h. The limit of detection was 0.3 micrograms/ml and the required amount of sample was 0.1 ml. When both diquat and paraquat were present in a sample the diquat was first extracted with 1-butanol prior to the ESR measurement, because both species were converted to the radicals.

Diquat↗

Continuous epidural infusion for postoperative pain relief: a comparison of three regimens.

We evaluated the postoperative pain relief and side-effects of continuous epidural infusion of three analgesic regimens following major thoracic and/or abdominal surgery. One hundred and twenty patients were randomly divided into three treatment groups: (1) 0.25% or 0.5% bupivacaine at a rate of 3-7 ml.hr(-1), (2) 0.01% morphine at a rate of 1-2 ml.hr(-1), (3) a combination of 0.125% or 0.25% bupivacaine and 0.0025% or 0.005% morphine at a rate of 2-4 ml.hr(-1). The study continued for the first 48 postoperative hours. The effect of pain relief was evaluated by assessment of the further requirement for parenteral analgesics. Sixty-four percent of the patients given bupivacaine, 56% of the patients given morphine and 80% of the patients given the combination required no supplemental analgesics. Continuous epidural infusion of bupivacaine was associated with hypotension (21%) and with numbness and weakness of hands or legs (18%). Continuous epidural infusion of morphine was associated with pruritus (18%) and with peristaltic depression (12%). The combination regimen was associated with pruritus (17%) and with drowsiness (14%). We conclude that the combination of bupivacaine and morphine significantly provides superior analgesia with less deleterious complications compared with either bupivacaine or morphine alone.

Clinical Trial↗

Continuous epidural infusion for postoperative mechanical ventilation.

We evaluated in analgesic and sedative effects of continuous epidural infusion of two analgesic regimens in ventilated patients following esophagectomy. Forty-six patients, divided into two treatment groups, received postoperative continuous epidural infusion of morphine, or that of a combination of bupivacaine and morphine. Assessments were made with the following indices: pain relief score, somnolence score, patient ventilator coordination score, and the number of supplemental administrations of analgesics and sedatives. No significant differences occurred in somnolence scores or patient ventilator coordination scores between the two groups, which revealed satisfactory sedation for mechanical ventilation. Patients receiving the combination of bupivacaine and morphine had significantly less pain postoperatively, requiring a smaller number of supplemental administrations of analgesics and sedatives ( P < 0.05). It is concluded that: 1) continuous epidural infusion of analgesics gives potent analgesia and sedation of ventilated patients following esophagectomy; 2) the combination of bupivacaine and morphine gives pain relief superior to morphine alone.

Journal Article↗

Changes in pulmonary function during continuous epidural bupivacaine with or without morphine following upper abdominal surgery.

To assess the effect of postoperative continuous thoracic epidural infusion of bupivacaine on pulmonary function, a prospective randomized study was conducted in patients undergoing upper abdominal surgery (UAS). Sixteen patients, divided into two treatment groups, received continuous epidural infusion of 0.25% bupivacaine at a rate of 2-5 ml.hr(-1), or that of a combination of 0.125% or 0.25% bupivacaine and 0.0025% or 0.005% morphine at a rate of 2-4 ml.hr(-1). One, 4, 10, 16, 24 and 40 hr postoperatively, the following indices were measured: visual analogue scale score, modified Prince Henry pain scale score, arterial Pa(O)(2) and Pa(CO)(2), functional residual capacity (FRC), and tidal volume (TV). There was no difference in pain scores between the two groups except for significantly less pain at 40 hr in the combination group. Postoperative measurements of pulmonary function revealed a significant fall in Pa(O)(2), FRC and TV, indicating a reduction of 15-25% as compared with the preoperative values, and no significant differences between the two groups. The authors conclude that postoperative continuous epidural infusion of bupivacaine combined with morphine is highly effective in alleviating pain and improving pulmonary function in patients following USA.

Clinical Trial↗