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Biomedical subjects

T Deguchi

Publications and source records attributed to T Deguchi.

At least 325 records · Page 18Linked to original sources
PubMed1983

[Safety evaluation of micronomicin IX. Perinatal and postnatal study by intravenous injection in rats].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Perinatal and postnatal studies of MCR in rats were carried out by intravenous injection for safety evaluation (Dose; 25, 50 mg/kg and 75 mg/kg). The results of studies are as follows. There was no adverse effect on delivery and nursing ability in dams at any dose. There was no adverse effect at any dose on postnatal development of offspring, such as weight gain, postnatal differentiation, spontaneous motor activity, learning, sexual maturation and reproductive performance. Renal toxicity was observed at dose of 75 mg/kg in autopsy of dams after treatment.

Aminoglycosides↗
PubMed1983

[Pharmacokinetic studies on micronomicin in rats. Comparison of intramuscular and drip intravenous administration models].

Absorption, tissue distribution and excretion of micronomicin (MCR) were studied in rats after intramuscular or 30 minutes drip intravenous administration (10 mg/kg). Serum levels of MCR were measured by bioassay, enzyme immunoassay and high pressure liquid chromatography. The pharmacokinetic studies of MCR after intramuscular or drip intravenous administration were carried out using one-compartment open model or two-compartment open model, respectively. Among 3 assay methods, similar pharmacokinetic parameters of MCR were obtained. In the simulation of serum levels of MCR, the differences between the measured and calculated serum levels after intramuscular or drip intravenous administration were less than 19% of the former levels. After intramuscular or drip intravenous administration of MCR, similar changes of the organ (kidneys, lungs, spleen and liver) levels were observed. Urinary recovery rates of MCR amounted to 82.3% or 91.6% by 24 hours after intramuscular or drip intravenous administration, respectively. After intramuscular or drip intravenous administration of MCR, no metabolites were found in urine of rats.

Aminoglycosides↗
PubMed1983

[Pharmacokinetic studies on micronomicin in dogs. Comparison of intramuscular and drip intravenous administration models].

The pharmacokinetics of micronomicin (MCR) were studied in dogs after intramuscular (i.m.) and drip intravenous (d.i.v., 0.5, 1 and 2 hours) administration (10 mg/kg). After i.m. administration, the plasma levels of MCR followed a one-compartment open model, and after d.i.v. administration it followed a two-compartment open model. The peak plasma levels of MCR after i.m., 0.5, 1 and 2 hours d.i.v. administration were 28.7 +/- 6.5, 36.7 +/- 3.6, 30.2 +/- 5.1 and 20.3 +/- 2.3 mcg/ml, respectively. The pharmacokinetic parameters (T1/2, AUC, Kel, Vd and Cl) of MCR except Cmax and Tmax were not differentiated by the route of administration. Urinary recovery of MCR after d.i.v. administration was equal to that of MCR after i.m. administration.

Aminoglycosides↗
PubMed1983

[A case of paraganglioma of the urinary bladder].

Herein we report a case of primary paraganglioma of the urinary bladder. A 21-year-old woman was admitted to an emergency hospital, because of gross hematuria, dysuria and complete urinary retention. Pelvic CT scan and ultrasonic examination revealed a bladder tumor and coagulated blood mass, then she was referred to our clinic for further treatment. On cystoscopy a dark brown lobular tumor was seen on the anterior wall. The bladder tumor was removed by partial cystectomy. The operative specimen measured 6 X 4 X 3 cm and weighed 50 g. Histological examination showed it to be a paraganglioma of the urinary bladder, which was chromaffin positive. Her serum and urinary catecholamine level were within the normal range after operation. She is now ten months postoperative, free from hematuria, and showing no other symptoms or signs of disease including metastasis.

Adult↗
PubMed1982

L-Arginine identified as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells.

Guanylate cyclase in neuroblastoma N1E 115 cells was readily solubilized upon homogenization of the cells with hypotonic buffer. When the supernatant was passed through cation exchangers such as a Chelex 100 Na+ column, the guanylate cyclase activity in the effluent fraction decreased to 4-6% of the original supernatant. The addition of the acid extract of neuroblastoma cells or rat tissues to the effluent restored guanylate cyclase activity, indicating that the supernatant of neuroblastoma cells contained an acid-soluble endogenous activator for guanylate cyclase which was adsorbed on cation exchangers. The activator was purified from rat brain and identified as L-arginine by 13C- and 1H-NMR spectroscopy and paper partition chromatography. L-Arginine, at a concentration of 1-2 x 10(-5) M, stimulated guanylate cyclase activity in the effluent fraction 15-25-fold, whereas D-arginine and other basic L-amino acids were ineffective. Peptides that contained L-arginine at the NH2- or COOH-terminal also resulted in an activation of guanylate cyclase to the extent similar to that of L-arginine, while peptides that contained L-arginine inside the peptide chain failed to stimulate the activity. The activation of L-arginine seemed to operate by a mechanism similar to that induced by nitroso compounds.

Animals↗
PubMed1982

Sympathetic regulation of circadian rhythm of serotonin N-acetyltransferase activity in pineal gland of infant rat.

The circadian rhythms of serotonin N-acetyltransferase activity in the pineal glands of infant and adult rats were compared. The nighttime increase of N-acetyltransferase activity in the pineals of infant rats was blocked by removal of superior cervical ganglion or by pretreatment with reserpine, l-propranolol, and cycloheximide. Injection of isoproterenol to infant rats markedly elevated pineal N-acetyltransferase activity. When the pineal glands of infant rats were organ-cultured, N-acetyltransferase activity spontaneously increased 7--12 h after the rats were killed. When infant rats were previously denervated or pretreated with reserpine and their pineals were cultured, this spontaneous elevation of N-acetyltransferase activity was abolished, indicating that the transient increase of the enzyme activity in organ culture was due to a liberation of catecholamine from degenerating nerve endings. Additional illumination until midnight prevented the nighttime increase of N-acetyltransferase activity in intact infant rats but not in blinded infant rats. These observations are taken to indicate that N-acetyltransferase rhythm in immature rat pineals is regulated by the sympathetic nerves in the same manner as in adult rat pineals, that the immature rat pineal does not contain a time-keeping system, and that there is no extraretinal light perception in infant rats as far as N-acetyltransferase rhythm is concerned.

Acetyltransferases↗
PubMed1982

[Studies on the physiological disposition and pharmacokinetics of 7-N-(p-hydroxyphenyl)-mitomycin C].

A new mitomycin derivative, 7-N-(p-hydroxyphenyl)-mitomycin C (KW 2083), was labeled with 14C at 3 and 5 position of p-hydroxyphenyl moiety. Its radioactive purity and specific radioactivity were 97.6% and 3.42 mu Ci/mg, respectively. The labeled drug was administered intravenously to male rats or pregnant rats. Radioactivity was rapidly cleared from the plasma and transferred to the peripheral tissues. However low and sustained level of radioactivity was maintained in the plasma, even 48 to 72 hours after administration. About 29% of the radioactivity was recovered from the urine and 58% from the feces by 72 hours after administration. In the bile, 45% of the dose was excreted until 48 hours after administration, and the enterohepatic circulation was observed. The tissue levels of 14C-KW 2083 given to male rats were highest in the kidney, liver and intestinal contents. In the brain, eyes and spinal cord the radioactivity was very low. Autoradiography with 14C-KW 2083 in male or pregnant rats demonstrated that radioactivity distributed in kidney, liver and intestinal contents. The transfer of radioactivity was very low in the fetuses of rats. Radioactivity was observed to some extent in the fetal membrane. Plasma concentrations of KW 2083 or mitomycin C in dogs were determined by means of bioactivity and could be best described by a two-compartment open model. The total clearance of KW 2083 was higher than mitomycin C and hence the biological half life of KW 2083 was shorter. The result may suggest less toxicity of KW 2083 to the host cells.

Animals↗
PubMed1982

[The pharmacokinetic studies on spiramycin and acetylspiramycin in rats].

Spiramycin (SPM) and acetylspiramycin (ASPM) have been known to be potent macrolide antibiotics in vivo, although spiramycins had rather mild antimicrobial activities in vitro. The physiological disposition of SPM and ASPM could participate in their in vivo activities. 14C-labeled SPM-I or 3H-labeled ASPM was administered intravenously in rats (20 mg/kg), and plasma levels, excretion and distribution have been studied. The plasma levels of SPM-I and ASPM were low both in radioactivity and bioactivity. After intravenous administration, 14C-SPM-I was excreted by 48 hours into urine, bile and faeces at the rates of 39.6, 31.4% and 37.1%, respectively. And 27.8% of the dose was recovered into urine by 48 hours after administration of 3H-ASPM. Higher radioactivities were detected in the spleen, kidney cortex, submaxillary gland, liver and lung by whole body autoradiography 1 hour after intravenous administration, and the levels tended to be retained until 24 hours. After intravenous administration at the dose rate of 50 mg/kg, the biological half-lives (T 1/2) of ASPM,SPM-I, josamycin and midecamycin were 151, 103, 71 minutes and 54 minutes, respectively, and the apparent volumes of distribution (V beta) were 9.2, 8.9, 3.6 L/kg and 7.7 L/kg, respectively. From these results, it was suggested that the highest activity observed for ASPM in experimental mice infections might be correlated with high affinity for the tissues and the long biological half-life of ASPM.

Animals↗
PubMed1981

Stimulation of phosphatidic acid of calcium influx and cyclic GMP synthesis in neuroblastoma cells.

Phosphatidic acid added to the medium markedly elevated intracellular cyclic GMP content in cultured neuroblastoma N1E 115 cells. There was a significant elevation of cyclic GMP with 1 micrograms/ml and a maximum (70-fold) elevation with 100 micrograms/ml of phosphatidic acid. Other natural phospholipids did not increase, or increased only slightly, the cyclic GMP content in the cells. The elevation of cyclic GMP content by phosphatidic acid was absolutely dependent on extracellular calcium. Phosphatidic acid stimulated the influx of calcium into neuroblastoma cells 2- to 5-fold. The pattern of the calcium influx induced by phosphatidic acid was comparable to that of cyclic GMP elevation. The stimulation of calcium influx by phosphatidic acid was also observed in cultured heart cells, indicating that phosphatidic acid acts as a calcium ionophore or opens a specific calcium-gate in a variety of cell membranes. Treatment of neuroblastoma cells with phospholipase C increased 32Pi labeling of phosphatidic acid, stimulated the influx of calcium, and elevated the cyclic GMP content in the cells. Thus exogenous as well as endogenous phosphatidic acid stimulates the translocation of calcium across cell membranes and, as a consequence, induces the synthesis of cyclic GMP in the neuroblastoma cells.

Animals↗
PubMed1981

Rhodopsin-like photosensitivity of isolated chicken pineal gland.

The pineal gland of lower vertebrates such as fish, amphibians and reptiles is primarily a photoreceptor organ and its electrical activity changes in response to environmental lighting, whereas the mammalian pineal gland is a secretory organ and no longer responds to direct illumination. It is uncertain whether the avian pineal gland retains a photoreceptive capability, and also whether the gland is a photosensor involved in the photo-periodic control of reproductive systems and circadian rhythms in birds. Recently, I and other workers have shown that the circadian rhythm of serotonin N-acetyltransferase activity persisted in organ cultures of chicken pineals, indicating the presence of an endogenous circadian oscillator in the gland. Also, the observation that direct illumination of cultured chicken pineals suppressed the night-time increase of N-acetyl-transferase activity suggests that the gland contains a photoreceptor. I report here that the action spectrum of the photosensitivity of the isolated chicken pineal resembles the absorption spectrum of rhodopsin.

Animals↗
PubMed1981

Effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492), a new phenylalanine derivative on lipid synthesis in vivo, inhibition of hepatic cholesterol synthesis and 3-hydroxy-3-methylglutaryl-Co A reductase.

KF 1492, a new phenylalanine derivative, was administered at a dose of 100 mg/kg or 0.25% (w/w) diet to Wistar rats. After different periods of drug administration, incorporation of 14 C-acetate or 14 C-mevalonic acid into digitonin-precipitable sterols and hepatic 3-hydroxy-3-methylglutaryl-Co A (HMG-CoA) reductase activity were measured. KF 1492 feeding was associated with depressed incorporation of 14 C-acetate into sterols in liver slices or homogenate. There was no effect on incorporation of 14 C-mevalonic acid into sterols. Thus, KF 1492 administration induced inhibition of hepatic HMG-CoA reductase correlated with reduction of incorporation of 14 C-acetate into digitonin-precipitable sterols. KF 1492 feeding also inhibited in vivo sterol synthesis in rats, which was intraperitoneally injected with 14 C-acetate. Stereoisomers, metabolites adn chemically similar compounds of KF 1492 reduced HMG-CoA reductase activity, and this was correlated with lowering the activity of plasma cholesterol. These findings indicate that a major site of the action of KF 1492 in the inhibition of sterol synthesis may be at the level of HMG-CoA reductase.

Animals↗
PubMed1981

Disturbance of serum lipid metabolism in acute renal failure.

Serial studies of serum lipids were performed on five patients with acute renal failure (ARF) due to five different causes (Of five patients one did not achieve complete recovery.). There were striking alterations in serum lipid levels at the period of oliguria in all patients, characterized by an increase in triglycerides (TG) and an extreme decrease in HDL-cholesterol (HDL-C). These conditions gradually returned to normal as the patients improved. The restoration to normal of the altered lipid levels were preceded by normalization of serum creatinine (S-Cr) and followed by creatinine clearance (Ccr). These fluctuational patterns of the lipid levels in the course of illness were observed similarly in all patients who recovered, despite the difference in the cause of their diseases. Improvement of the lipid metabolism was not observed in the one patient who did not recover. These results suggest that the alteration in lipid metabolism of ARF is due to renal impairment and not related to uremic state per se.

Acute Kidney Injury↗