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Biomedical subjects

T Mashimo

Publications and source records attributed to T Mashimo.

At least 145 records · Page 8Linked to original sources

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↗

In vivo characteristics of low molecular weight copoly (D,L-lactic acid) formulations with controlled release of LH-RH agonist.

Amorphous and crystalline copolymers with a relatively low molecular weight of 1800 were synthesized by direct copolycondensation of D-lactic acid and L-lactic acid in the absence of a catalyst, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide, was incorporated in a fine cylindrical copolymer formulation, under melt-pressing technique, a mild heat-pressure condition. This formulation was implanted subcutaneously in the back of male rats. The rate of in vivo degradation of amorphous copolymer was much faster than that of crystalline copolymer. Contrary to this tendency, the in vivo release of the drug from this amorphous formulation was held constant over a longer period, compared with the crystalline formulation. This can be closely related to the difference in dispersion of the drug in the formulation.

Animals↗

Effects of carboxyhemoglobin on pulse oximetry in humans.

Carboxyhemoglobin (HbCO)-induced reading errors of the Biox 3700 (version J, Ohmeda) pulse oximeter were determined in 6 healthy volunteers rendered hypoxic (Sa(O)(2) from 65-100%) by breathing mixtures of air in nitrogen. The oximeter reading (Sp(O)(2)) before and after cigarette smoking was compared with oxyhemoglobin percentage (%HbO(2)). Mean HbCO levels were; 3.0 +/- 1.0 (SD) % before cigarette smoking and 5.2 +/- 1.7% after smoking, whereas mean methemoglobin was unchanged as 0.5 +/- 0.1%. The correlations of the Sp(O)(2) (y) with %HbO(2) (x) were; y = 1.01x - 0.30 (r = 0.990, n = 21, P < 0.001) when %HbCO was less than 2.5, and y = 1.01x + + 3.21 (r = 0.964, n = 33, P < 0.001) when %HbCO was above 5.0%. The reading error, (Sp(O)(2) - %HbO(2)), could be expressed as a function of %HbCO; 1.06 x %HbCO(2) - 2.49 (r = 0.669, n = 83, P < 0.05). Thus, the Sp(O)(2) is approximately the sum of %HbCO(2) and (%HbCO - 2.5), and overestimates %HbO(2) in the high levels of HbCO. The pulse oximeter should be used with caution in patients with the elevated level of %HbCO.

Journal Article↗

[An adenoid tumor of the epididymis--electron microscopy and immunohistochemistry].

A case of an adenomatoid tumor of the epididymis is reported. The patient, a 41-year-old male, had a total right orchiectomy of his testicular mass. The tumor was located in the inferior portion of the right epididymis and was a well-circumscribed solitary mass, measuring 3 X 3 X 3 cm. Microscopically, the tumor contained plump acidophilic cells arrange in cords and trabecula with fibrous connective tissue. Immunohistochemical studies for keratin and vimentin in the tumor cells were positive. Electron microscopical findings of the tumor were similar to those of a benign mesothelioma. These findings suggest that adenomatoid tumors are of mesothelial origin.

Adult↗

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↗

Electroretinogram as a possible monitor of anesthetic depth.

The effects of volatile anesthetics, i.e., methoxyflurane, halothane and enflurane, on the electroretinogram (ERG) were studied in 15 albino rabbits. The ERG was analyzed in terms of the a-wave, and the first oscillatory component (01) in the b-wave. The 01 peak latency showed a significant dose-related prolongation when anesthetic end-tidal concentrations were in excess of 0.8 minimum alveolar concentration (MAC). One MAC, a measure of anesthetic potency, is the end-tidal concentration of an anesthetic at 1 atmosphere that induces immobility in 50% of animals against a noxious stimulus. The amplitudes of the a-wave and the 01 decreased in dose-dependent manners, but their changes were less striking than those of the 01 latency. The peak latency of the a-wave remained unchanged. We conclude that the 01 peak latency is a useful monitor of the depth of inhalational anesthesia.

Anesthesia↗

Dual effect of local anesthetics on the function of excitable rod outer segment disk membrane.

The effects of local anesthetics and a divalent cation, Ca2+, on the function of rhodopsin were estimated from the measurements of light-induced proton uptake. The light-induced proton uptake by rhodopsin in the rod outer segment disk membrane was enhanced at lower pH (4) but depressed at higher pHs (6 to 8) by the tertiary amine local anesthetics lidocaine, bupivacaine, tetracaine, and dibucaine. The order of local anesthetic-induced depression of the proton uptake followed that of their clinical anesthetic potencies. The depression of the proton uptake versus the concentration of the uncharged form of local anesthetic nearly describes the same curve for small and large dose of added anesthetic. Furthermore, a neutral local anesthetic, benzocaine, depressed the proton uptake at all pHs between 4 and 7. These results indicate that the depression of the proton uptake is due to the effect of only the uncharged form. It is hypothesized that the uncharged form of local anesthetics interacts hydrophobically with the rhodopsin in the disk membrane. The dual effect of local anesthetics on the proton uptake, on the other hand, suggests that the activation of the function of rhodopsin may be caused by the charged form. There was no significant change in the light-induced proton uptake by rhodopsin when 1 mM of Ca2+ was introduced into the disk membrane at varying pHs in the absence or presence of local anesthetics. This fact indicates that Ca2+ ion does not influence the diprotonating process of metarhodopsin; neither does it interfere with the local anesthetic-induced changes in the rhodopsin molecule.

Anesthetics, Local↗

[Clinical evaluation of norfloxacin in gonococcal urethritis].

Norfloxacin, a new quinolinecarboxylic acid derivative, was administered to 30 male patients with gonococcal urethritis at a daily dose of 600 mg for 7-21 days. The clinical response was evaluated after administration of 7 days as excellent; Negative culture of N. gonorrhoeae. WBC less than 3/hpf in first voided urine sediment, good; Negative culture, WBC greater than or equal to 3/hpf, and poor; Positive culture. The result was excellent in 14 cases and good in 16 cases. No subjective side effects were observed. The minimum inhibitory concentration (MIC) distribution against the clinically isolated 30 strains of N. gonorrhoeae ranged from 0.0096 micrograms/ml to 0.34 micrograms/ml. Seven of thirty strains were resistant to ABPC. The MIC of these 7 strains ranged from 0.018 micrograms/ml to 0.18 micrograms/ml. Seven cases with ABPC resistant strains had a similar clinical response to other cases. Twelve patients (40%) developed post gonococcal urethritis for 7-14 days after treatment. Clinical observation of this series suggests that a 7 day therapy of Norfloxacin for the patients with gonococcal urethritis is sufficiently effective and that treatment should be changed to other antibacterial agents in the case of post gonococcal urethritis, since continuous administration for more than 7 days of Norfloxacin is not so effective.

Adult↗

Anesthetic-protein interaction: surface potential of bovine serum albumin estimated by a pH-sensitive dye.

It is often contended that inhalation anesthetics act on proteins via perturbation of lipid membranes. However, direct interaction between anesthetics and water-soluble proteins also has been demonstrated. We postulate that the anesthetic action is directed to the interface between water and macromolecules, irrespective of lipid membranes or proteins. The present study deals with anesthetic effects upon interfacial properties of a water-soluble, crystalline delipidated bovine serum albumin. A pH-indicator dye, bromothymol blue, was used to probe the surface potential of the protein. When a pH-indicator dye binds to a macromolecule, the pH, indicated by the color of the dye, differs from the bulk pH measured by a pH meter. This is because the pH of the microscopic area, where the dye is adsorbed, differs from the bulk due to the surface electrostatic potential that interacts with hydrogen ions (electrostatic terms), and the physical property that affects the color of the dye at the bound region is different from the bulk (nonelectrostatic terms). The mismatch between the bulk pH and the color of the bound pH indicator can be used to probe the property of the dye binding site. By screening the electrostatic effects with high ionic strength, the anesthetic effects upon the nonelectrostatic term were shown to be negligible under the present experimental conditions; the pH-color mismatch was mainly caused by the anesthetic effect upon the electrostatic potential of the macromolecular surface interacting with the dye. Accordingly, the surface potential of the dye binding site was estimated from the mismatch. It was found that inhalation anesthetics decreased the surface potential. The partial pressures of diethylether, enflurane, and methoxyflurane that decreased the surface potential by 10 mV were 2.1 X 10(-2), 1.7 X 10(-2), and 0.17 X 10(-2) bar, respectively, which were in agreement with the minimal alveolar concentrations of these anesthetics to achieve surgical anesthesia.

Anesthesia, Inhalation↗

Volatile anesthetics cause conformational changes of bacteriorhodopsin in purple membrane.

We examined the effects of volatile anesthetics on the structure of the bacteriorhodopsin in the purple membrane by measurements of the absorption spectrum and the visible circular dichroism (CD) spectrum and assay of the retinal composition. As the concentrations of halothane, enflurane and methoxyflurane were increased, the absorption at 560 nm decreased but that at 480 nm increased with an isosbestic point around 510 nm. These anesthetic-induced spectroscopic changes were reversible. The CD spectrum showed the biphasic pattern with a positive and a negative band. As the concentration of halothane was increased from 4 mM to 8mM, the negative band reversibly diminished more drastically than the positive band, and at 8 mM of halothane the positive band shifted to around 480 nm. These results show that halothane disturbed the exciton coupling among bacteriorhodopsin molecules. The retinal isomer composition was analyzed using high performance liquid chromatography. The ratio of 13-cis- to all-trans-retinal was 47:53, 34:66 and 19:81 at control, 7.4 mM and 14.9 mM enflurane, respectively. After elimination of enflurane, the ratio returned to the control value. These findings indicate that volatile anesthetic directly affect a bacteriorhodopsin in the purple membrane and induce conformational changes in it.

Anesthetics↗

Blood glucose control by an artificial endocrine pancreas in a patient with phaeochromocytoma.

In a patient with phaeochromocytoma who presented with unstable diabetes mellitus, an artificial endocrine pancreas was used intraoperatively. Anaesthetic agents included enflurane, nitrous oxide and oxygen. Nicardipine was used to control hypertensive episodes. The initial blood glucose concentration was 173 mg X dl-1 and it decreased to 110 mg X dl-1 in response to insulin infusion, but plasma catecholamines were markedly increased. Seventy minutes later, the glucose concentration increased progressively to 249 mg X dl-1 despite massive insulin infusion, maximally 5.64 mU X kg-1 X min-1. The blood glucose concentration reached a peak at the time of the ligation of the venous drainage from the tumour and the peak was coincident with that of plasma catecholamine levels (epinephrine: 20.8 ng X ml-1, norepinephrine 16.4 ng X ml-1). Both glucose and catecholamine concentrations decreased promptly after removal of the tumour and hypotension followed likely because of a persistent vasodilatatory effect of nicardipine. The profiles of blood glucose, insulin and glucose infusion rates provided by the artificial endocrine pancreas suggested that the insulin resistance began to be reversed shortly after removal of the phaeochromocytoma.

Adrenal Gland Neoplasms↗