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T Mashimo

Publications and source records attributed to T Mashimo.

At least 37 records · Page 2Linked to original sources

The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy.

Anaesthetic concentration is very important for the quantitative treatment of anaesthesia theory. Traditionally concentration values have been derived from the water/gas partition coefficient. However, the values from many investigators show discrepancies. This study reports the accurate solubility of methoxyflurane (9.1 mM), halothane (18.0 mM), enflurane (11.9 mM) and isoflurane (13.5 mM) in water at 25.0 degrees C using 19F NMR spectroscopy. The method has advantages in that the dissolved molecule in solution can be separately quantified from undissolved anaesthetic. Saturated solutions of the anaesthetic agents were prepared in situ in a NMR tube to avoid pressure and temperature changes in the solution.

Anesthetics

Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine.

The purpose of our study was to produce a long-acting lidocaine by using a liposome that would entrap the drug. Egg yolk phosphatidylcholine and cholesterol were used as liposome materials. After epidural administration, the pharmacodynamics and pharmacokinetics of liposomal and free lidocaine were studied in 20 dogs. Two percent liposomal or free lidocaine (3.0 mL) was injected into the lumbar epidural space. Nerve blocking effects were estimated by measuring somatosensory evoked potentials. Recovery time from the epidural block in the liposomal lidocaine group (170 +/- 49.5 min) was approximately three times longer than that in the free lidocaine group (61 +/- 18.1 min). The areas under the drug concentration-time curves (AUC0-infinity) and time to maximal concentration (Tmax) in the liposomal lidocaine group were significantly larger than those in the free lidocaine group. These results suggest that the prolongation of epidural blockade by liposomal lidocaine is caused by a slow release of the drug from liposomes. The present study suggests that liposomal lidocaine can be used as a long-acting local anesthetic.

Amines

Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans.

To clarify the site of action of epidural fentanyl, we compared the effects of epidural and intravenous fentanyl on the change in pressure pain threshold (PPT) and the minimum alveolar concentration (MAC) of halothane. Seventy patients who underwent gastrectomy in the PPT study group and 84 female patients who underwent hysterectomy in the MAC study group were assigned randomly to seven groups in each study. The seven groups each received a bolus injection of 1, 2, or 4 micrograms/kg of fentanyl, either intravenously or epidurally, and of saline solution epidurally. Compared with intravenous fentanyl, epidural fentanyl significantly increased (P less than 0.01) PPT around surgical incisions by approximately 50%, 100%, and 150% of preadministration levels 1 h after administration of 1, 2, and 4 micrograms/kg, respectively, and significantly reduced (P less than 0.05) halothane MAC at the same doses. These data suggest that the more potent analgesic and anesthetic effects of epidural fentanyl, compared with intravenous fentanyl, are due mainly to the segmental analgesia produced by its spinal analgesic action.

Adult

[Prostatic specific antigen (PA) in mass screening for prostate cancer].

The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test "TOSOH" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.

Acid Phosphatase

[Clinical effect of Cernilton in chronic prostatitis].

Twenty-five patients with chronic prostatitis were given Cernilton tablets. Improvement of subjective symptoms and objective findings was noted in 96.0% and 76.0% of the cases. Sonographic findings in the prostate showed 33-100% improvement in four objective items. No side effects were observed in any case after Cernilton medication. Cernilton was judged to be an effective drug for chronic prostatitis.

Administration, Oral

Sectional anatomy of the pelvis in the male rat with ultrasound correlations.

Ten-week-old male Wistar rats were used for sectional anatomy and ultrasonic diagnosis of the pelvis. The prostate and the urinary bladder were identified easily on longitudinal section by ultrasound examination. The prostate (ventral, lateral, and dorsal lobes) was located in the midline of the pelvis cavity on transverse sections and the caudal side of the urinary bladder on longitudinal sections. The urinary bladder was positioned at the cranial side of the prostate on longitudinal sections and in the midline of the pelvis cavity on transverse sections. The seminal vesicles were located at right and left positions of the urinary bladder. Ultrasonic diagnosis was estimated to be useful for experimental studies and we hope that ultrasound techniques may reduce the number of rats used for the treatment of prostate and urinary bladder cancers.

Animals

A new biodegradable copolymer of glycolic acid and lactones with relatively low molecular weight prepared by direct copolycondensation in the absence of catalysts.

Relatively low-molecular-weight copolyesters of glycolic acid (GA) with lactones such as gamma-butyrolactone (BL), delta-valerolactone (VL), and epsilon-caprolactone (CL) were synthesized by copolycondensation without catalysts. The resulting copolyesters are intended as carriers for drug delivery systems. Copolyesters with approximately 85 mol% GA (number-average molecular weight (Mn): 2900 +/- 100) are crystalline and solid and show a parabolic-type in vivo degradation pattern. The in vivo degradation of amorphous-pasty poly (GA/CL) (approximately 50/50 mol%) changed from parabolic-type to linear-type to S-type pattern as their molecular weight increased. A luteinizing hormone-releasing hormone agonist, [D-Leu6, des-Gly10]-LHRH ethylamide monoacetate (LHRH agonist), was incorporated into small cylinders with these copolyesters. An initial burst of LHRH agonist was observed for cylinders prepared with parabolic-type degrading copolyesters, in contrast to a marked delay in LHRH agonist release for cylinders prepared with S-type degrading copolyesters. The resulting daily dose of drug was maintained an approximately constant, though decreasing stepwise with time. For example, the daily amount of LHRH agonist released in vivo from a cylinder prepared with poly(GA/CL) (50/50 mol%; Mn = 4500) was 61 +/- 39 micrograms/day throughout an experimental period of 10 weeks with a corresponding pharmacological effect on the rat prostate.

Animals

In vivo characteristics of high molecular weight copoly(L-lactide/glycolide) with S-type degradation pattern for application in drug delivery systems.

Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates.

Animals

Effects of volatile anesthetics on bacteriorhodopsin in purple membrane, Halobacterium halobium cells and reconstituted vesicles.

In this study, we have investigated effects of volatile anesthetics on absorption spectra, proton pumping activity and decay of photointermediate M of bacteriorhodopsin (bR) in differently aggregated states. Anesthetics used in this study are ether-type general anesthetics; enflurane and sevoflurane. The observed effects on bR depend not only on variety or concentration of anesthetics but also strongly on the aggregation state of bR molecules in the membrane. In purple membrane (PM), bR having maximum light absorption at 567 nm (bR567) is formed in the presence of sevoflurane or a small amount of enflurane, while a species absorbing maximally at 480 nm (bR480) is formed upon the addition of large amounts of enflurane. X-ray diffraction studies show that the former species maintains crystallinity of PM, but the latter does not. In reconstituted vesicles where bR molecules exist as monomer, even sevoflurane forms bR480. Flash photolysis experiments show that bR567 contains a shorter-lived M intermediate absorbing maximally at 412 nm in the photoreaction cycle than bR does and that bR480 contains at least two long-lived M intermediates which seem to absorb maximally near and at lower than 380 nm. The measurements of light-induced pH changes of the whole cells and of the reconstituted vesicles in the presence of the anesthetics indicate that bR567 has a enhanced proton pumping efficiency, while bR480 has a quite low or no activity. No significant difference was observed in the anesthetic action between two inversely pumping vesicles. These observations suggest that on the formation of bR480, anesthetics enter into the membrane and affect the protein-lipid interaction.

Anesthetics

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

[Clinical analysis of male urethritis].

We reviewed 497 patients with male urethritis diagnosed between January, 1986 and March, 1989 at the Asama General Hospital. The incidence of gonococcal urethritis (GU) was 47.7%, and that of non-gonococcal urethritis (NGU) 52.3%. There was no difference in the age distribution between GU and NGU. Prostitutes were the most common source of the infection in both GU and NGU. Incubation periods were longer in NGU than in GU, statistically. Urethral discharge was the most common symptom. Purulent urethral discharge was seen more commonly than serous urethral discharge in GU. On the contrary, serous urethral discharge was more common in NGU. Penicillin-resistant gonococcus comprised 29.4% and mixed infection of the C. trachomatis existed 25.6% in GU. C. trachomatis was detected in 71.8% in NGU. In GU, new quinolones and penicillins were administered frequently. The effective rates 1 week after the administration were 80.6% and 83.3%, respectively. In NGU, new quinolones and minocycline were administered frequently. The effective rates were 70.4% and 85.3%, respectively. Ofloxacin (OFLX) showed the highest effective rate to NGU among the four new quinolones. The relapse rate for the two-week administration group was lower than that for the one-week-administration group, but the difference was not statistically significant.

Adolescent

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

The effect of prostaglandin E1 on local cerebral blood flow during cerebral-aneurysm clip ligation.

Prostaglandin E1(PGE1) was administered for deliberate hypotension during general anaesthesia in 27 patients undergoing cerebral-aneurysm clip ligation, and the effect of the drug on local cerebral blood flow was studied. Local cerebral blood flow measurements were made using a thermal-gradient blood flowmeter. Control measurements were made immediately before administration of the drug. Local cerebral blood flow was measured 10, 30, 60 and 120 min after starting the drug infusion and 10, 30 and 60 min after discontinuation. The mean blood pressure was reduced significantly by the administration of PGE1. Urine output was increased after commencement of the drug infusion. Local cerebral blood flow did not change. These results suggest that PGE1 may be an appropriate hypotensive drug for use during cerebral-aneurysm clip ligation, because the cerebral blood flow remains within the normal range and the urine output is increased.

Alprostadil

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

In vivo characteristics of low molecular weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers for drug delivery systems.

Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.

Animals