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Biomedical subjects

Y Fukagawa

Publications and source records attributed to Y Fukagawa.

At least 37 records · Page 2Linked to original sources
PubMed1990

Enhancement of morphine withdrawal signs in the rat after chronic treatment with naloxone.

Chronic treatment of rats with naloxone for 5 days increased the analgesic threshold (hot plate latency). Further, when rats were treated with morphine-admixed food for 3 days after the chronic naloxone treatment the withdrawal signs precipitated by naloxone were significantly greater in the naloxone-pretreated rats than in saline-pretreated rats. These results suggest that paradoxical analgesia and enhancement of the morphine withdrawal signs induced by chronic naloxone treatment may be associated mainly with up-regulation of mu- and delta-opioid binding sites in the central nervous system.

Analgesia↗
PubMed1990

"Paradoxical" analgesia and aggravated morphine dependence induced by opioid antagonists.

Chronic treatment with naloxone (Nx) or naltrexone (Ntx) induces paradoxical analgesia. In the present study, the effects of chronic treatment with opioid receptor antagonists, such as nor-binaltorphimine (nor-BNI) for kappa and naltrindole (NTI) for delta receptors, on analgesic response using the hot plate test and on morphine physical dependence in rats were examined. The hot plate latency was significantly increased by pretreatment with Nx (5 mg/kg, s.c.), nor-BNI (20 mg/kg, i.p.) or NTI (20 mg/kg, i.p.) for 5 days. After chronic pretreatment with these antagonists, the rats were treated with morphine-admixed food (0.5 mg/g of food) for 3 days. Chronic pretreatment with Nx and NTI significantly increased Nx precipitated body weight loss in morphine dependent rats, while chronic pretreatment with nor-BNI produced small increase. These results indicate that chronic treatment with nor-BNI or NTI as well as with Nx induces obviously paradoxical analgesia, and that chronic blockade of mu or delta may enhance the development of physical dependence on morphine.

Animals↗
PubMed1990

Antibacterial activity and chemical modifications of PS-5 at the C-3 side chain.

Using PS-5 as starting material, the effects of chemical modification at the C-3 side chain were studied on the antibacterial activity against Gram-positive and Gram-negative bacteria including beta-lactamase-producers. Among 35 side chains tested, 4-pyridylthio showed the highest antibacterial activity against the Gram-positive bacteria, and D-cysteinyl against the Gram-negative microbes. In general, compared with acetamidoethylthio in PS-5, basic side chains showed improved antibacterial activity against the staphylococci and pseudomonads, whereas the antibiotic activity against the Gram-negative bacteria decreased with bulky side chains. The introduction of 6-aminopenicillanate and 7-aminocephalosporanate to the C-3 side chain of carbapenem significantly reduced the antibacterial activity against the beta-lactamase-producing microbes.

Gram-Negative Bacteria↗
PubMed1990

[The effects of constituents of an antitussive and expectorant preparation on physical dependence on and antitussive activity of dihydrocodeine].

The effects of constituents of an antitussive and expectorant preparation on physical dependence potential and antitussive activity of dihydrocodeine (DC) were studied. Rats were treated with DC, methylephedrine (ME), chlorpheniramine (CP), and caffeine (CA) singly or simultaneously admixed with food (DC 0.125, ME: 0.25, CP: 0.05, CA: 0.25 mg /g of food) for 7 days. Subsequently, rats were treated with naloxone (0.5 mg/kg, sc) and withdrawal signs produced were observed. Naloxone-precipitated body weight loss in DC-treated rats was suppressed by simultaneous administration of the three drugs (ME, CP and CA) or CP, which is a H1-receptor antagonist. In abrupt withdrawal, the withdrawal signs were also suppressed by CP. Moreover, tripelennamine, the same kind of H1-receptor antagonist, suppressed naloxone-precipitated withdrawal signs, but cimetidine H2-receptor antagonist, did not suppress them. These results may suggest that H1-receptor antagonists suppress the development of physical dependence on DC, and that H1-receptors play an important role in the physical dependence. On the other hand, the cough reflex was induced by electric stimulation in order to evaluate the influence of ME, CP, and CA on antitussive effect of DC in guinea pigs. ME enhanced the effect of DC. These experimental findings suggest that the constituents of the antitussive and expectorant preparation suppress the development of physical dependence on DC, though they increase the antitussive effect of DC.

Animals↗
PubMed1990

[Pharmacogenetic studies on analgesic activity of and physical dependence on morphine in BALB/c, C57BL/6 inbred mice and these recombinant CBF1 mice].

Mice of the BALB/c, C57BL/6, and CBF1 strains were studied with respect to analgesic activity of and physical dependence on morphine. The acute administration of morphine resulted in analgesic response in the three strains with the following ranking orders: BALB/c greater than C57BL/6 = CBF1 for 5 mg/kg, and C57BL/6 greater than BALB/c greater than CBF1 for 10 and 20 mg/kg. Mice were treated with morphine-admixed food (1-3 mg/g of food) for 9 days. During the treatment, morphine intake in BALB/c was lower than those in C57BL/6 and CBF1. Thus, we examined the degree of physical dependence in three mouse strains after chronic morphine injections for 10 days. There was significant difference in naloxone-precipitated body weight loss among strains, the ranking being as follows: BALB/c greater than CBF1 greater than C57BL/6. However, there was no difference in appearance rate of naloxone-precipitated jumping, but a difference in body shakes and body weight loss, among strains. These results suggest that analgesia of and preference for morphine, and naloxone-precipitated weight loss and body shakes may be influenced by genetic factors.

Administration, Oral↗
PubMed1989

Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats.

Rats were made dependent on morphine by mixing the drug with their only source of food. Naltrexone (0.5 mg/kg) injection precipitated a syndrome of withdrawal signs including weight loss. Pretreatment with the selective kappa agonist, U-50,488H (1.0, 30.0 or 10.0 mg/kg), generally had no effects on the signs of morphine withdrawal. In other subjects, U-50,488H was repeatedly administered (1.0, 3.0 or 10.0 mg/kg per 12 h) during the development of morphine dependence. In these subjects, the course of naltrexone-precipitated withdrawal was unchanged. These results suggest that agonist activity at kappa receptors is not sufficient to alter morphine dependence or withdrawal.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Modification of the effects of naloxone in morphine-dependent mice.

Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.

Analgesia↗
PubMed1988

Effect of opioid agonist-antagonist interaction on morphine dependence in rats.

Morphine dependence was induced by treatment with morphine-admixed food (0.25mg/g of food) for 7 days. Withdrawal was precipitated by injecting naloxone (0.5mg/kg, s.c.). Rats treated with morphine exhibited body weight loss upon the naloxone injection. When morphine-dependent rats were injected subcutaneously with morphine, codeine, meperidine and pentazocine 30 min before the naloxone injection, these drugs significantly suppressed the naloxone-precipitated loss of body weight in a dose-dependent manner. However, body weight loss induced through coadministration of naloxone and Mr-2266 BS were not suppressed by morphine pretreatment. These results suggest that opioids protect against naloxone-precipitated loss of body weight, and that mu and kappa opiate receptors play an important role in the protection against naloxone-precipitated withdrawal.

Animals↗
PubMed1988

Synthesis and structure-activity studies of new 4''-O-acyltylosin derivatives of therapeutic interest.

Eleven 4''-O-acyltylosin derivatives were synthesized and subjected to a two-step screening system consisting of antimicrobial activity and esterase stability assays. The new derivatives were all active against macrolide-resistant Staphylococci and mycoplasmas, but only 4''-O-(4-methoxy)phenylacetyltylosin and 4''-O-(4-acetyl)phenylacetyltylosin showed better resistance to mouse liver esterase than 4''-O-phenylacetyltylosin (reference compound C).

Animals↗
PubMed1988

Mutagenesis of OA-6129 carbapenem-producing blocked mutants and the biosynthesis of carbapenems.

Streptomyces fulvoviridis A933 17M9 1501 is an A933 acylase-defective mutant derived from S. fulvoviridis A933 17M9 and thus produces the OA-6129 group of carbapenems and carbapenams. By further mutation of mutant 1501, 4 types of mutants (OA-6129 A + B1 + B2 producers; OA-6129 A + B2 producers; an OA-6129 A producer; non-producers) were obtained. The second type of mutant strains 4N 3607, 5NA 3949-40 and 5NE 252 proved useful for the fermentative production of carbapenem OA-6129 B2. These results of mutagenesis demonstrated that the sequence of carbapenem bioconversion in the horizontal route was hydroxylation at C-8----isomerization at C-6----sulfation at C-8 hydroxyl.

Mutation↗
PubMed1987

New tylosin analogs produced by mutants of Streptomyces fradiae.

2'''-Demethoxytylosin (component IIIc), 2'''-demethoxy-4'''-epi-tylosin (component IIId) and 2'''-O-demethyltylosin (component Vb) were produced by blocked mutant strains of Streptomyces fradiae. Fermentation, isolation, structure determination and biosynthetic considerations of these tylosin analogs are described.

Chemical Phenomena↗
PubMed1986

Analysis of capillary fluid flow rate by vibration on a small vessel model.

In order to estimate the direct effect of the physical vibration on the peripheral blood flow rate, we measured the water flow rate in a silicon capillary tube whose end was vibrated. Three types of vibration were added to the tube and the frequency of the vibration covered 1-2000 Hz. It is shown that the water flow rate reduces under the vibration and this reduction strongly depends on the frequency and the type of the vibration. The main reason for this dependence is shown to be as follows. The vibration stretches the tube and the average length of the tube is longer under the vibration than when under no vibration, and the average tube radius is smaller under the vibration. This causes the reduction of the flow rate under vibration. Because the stretch of the tube strongly depends on the frequency and the type of the vibration, the above dependence of the water flow rate finally appears.

Capillaries↗
PubMed1986

[Observations of capillary fluid flow rate by vibration on the small vessel model].

The vibration hazards in peripheral blood vessels as an occupational origin is caused by using pneumatic vibrating tools. In order to know that the major part of causes is whether due to the direct effects of the physical vibration or due to the effects depended on the excitations of peripheral nervous system, an model experiment was employed to estimate the direct effect of the physical vibration. In our experiments, water as fluid was used instead of blood. The silicon capillary tube as same the physical qualities and conditions as blood vessels was vibrated by oscillator. The silicon capillary tube was exposed by following three type of vibration mode to flow axis; i) sine wave of transverse vibration, ii) rectangular wave of transverse vibration, and iii) sine wave of longitudinal vibration. The range of vibration frequency covered 1-2000 Hz. The averaged acceleration by oscillating vibration and the vibration strength level were estimated about 1-200 G and 150 dB, respectively. The observed decreases of water flow rate due to vibration extremely depend on frequency. The decrease ratio of water flow rate by vibration was at maximum 12% down compare with the cases of non vibration. In these observed results by this model experiment, it should be concluded that the direct effect of the physical vibration to the blood flow was not too strong to cause the actual vibration hazards.

Blood Circulation↗