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Biomedical subjects

M Iigo

Publications and source records attributed to M Iigo.

126 records · Page 7Linked to original sources
PubMed1976

Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors.

Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil against various tumors was examined. Therapeutic ratio (ILSmax/ILS30) in L-1210 system was 4.5 by oral administration, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 1.9 and 1.0, respectively. Therapeutic ratio of the compound in C-1498 system was 11, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 3.3 and 2.5, respectively. 1-Hexylcarbamoyl-5-fluurouracil was also active against solid and ascites tumors by oral administration. It was markedly active against Nakahara-Fukuoka sarcoma, adenocarcinoma=755, and ascites sarcoma-180, and moderately active against Ehrlich ascites carcinoma. This compound had a wider tumor spectrum than 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil by oral administration.

Adenocarcinoma↗
PubMed1976

Antitumor activity of berberrubine derivatives.

The antitumor activity of berberine, berberrubine, and their derivatives against sarcoma-180 ascites was determined by the total packed cell volume method. Berbine and tetrahydroberberine derivatives had no antitumor activity, but berberrubine (9-demethylberberine) and the ester derivatives of berberrubine had a strong antitumor activity. ED90 of berberrubine, its acetate and benzoate, were 15, 23, and 44 mg/kg, respectively. The therapeutic indices (LD10/ED90 by the present method) of these compounds were as follows: Berberrubine hydrochloride, 6.7 approximately 9.4; 9-acetyl-9-demethylberberine (9-acetylberberrubine) chloride, 7.6 approximately 8.7; 9-benzoyl-9-demethylberberine (9-benzoylberberrubine) chloride, 3.4 approximately 4.9.

Animals↗
PubMed1975

Effect and toxicity of combination treatment including cyclocytidine or cytosine arabinoside in L-1210 and sarcoma-180 systems.

Combination effect of antitumor agents, including cyclocytidine and cytosine arabinoside, was evaluated on the conception of pharmacological synergism and not of therapeutic synergism. Ascites sarcoma-180 and L-1210 leukemia were used as tumor systems. In sarcoma-180 system, combinations of cyclophosphamide plus cyclocytidine or cytosine arabinoside by simultaneous administration and cyclocytidine plus Daunorubicin or Vinblastine by alternate administration provided synergism. In L-1210 system, many compounds in combination with cyclocytidine or cytosine arabinoside in both simultaneous and alternate administrations provided synergism. Combination effect of agents was affected by the schedule of drug administration. It was found that the combination effect of drugs in one tumor system cannot be generalized to that in other tumor systems, even though equally effective doses of agents were administered in both tumor systems. Toxicity of cytosine arabinoside in combination with other drugs was affected by the schedule of administration. Compounds which provided synergism in simultaneous administration provided antagonism in alternate one. As a result, it was found that alternate administration of drugs is advantageous for the activity and diminution of toxicity of the host animal.

Animals↗
PubMed1975

Antitumor activity of carbamoyl derivatives of 5-fluorouracil by oral administration.

Antitumor activity of 1-carbamoyl derivatives of 5-fluorouracil was tested in L-1210 system by oral administration with two reference compounds, 5-fluorouracil and tetrahydrofuryl-5-fluorouracil (FT-207). The compounds tested were methyl-, ethyl-, isopropyl-, phenyl-, and cyclohexyl-carbamoyl-5-fluorouracil, and the therapeutic ratios (ILSmax/ILS30) of these compounds were 1.9, 2.2, 2.3, 1.0, and greater than 3.3, respectively, those of the two reference compounds being 1.7 and 1.0. Cyclohexylcarbamoyl-5-fluorouracil was the most effective of these compounds.

Administration, Oral↗
PubMedDate not supplied

Female-soiled bedding induced fos immunoreactivity in the ventral part of the premammillary nucleus (PMv) of the male mouse.

Previous studies have indicated that the ventral part of the premammillary nucleus (PMv) of rodents is involved in the regulation of aggressive and male mating behavior, although the precise physiological function of the PMv is still unclear. To analyze the physiological role of the PMv in male mating behavior, the effects of exposure to bedding soiled by female mice on Fos immunoreactivity (Fos-ir), an early marker of neuronal activation, were studied in the PMv and some sex-related nuclei. We observed that exposure to female-soiled bedding induced Fos-ir expression in the PMv of the male mouse. Although Fos-ir positive cells were found in the posterodorsal part of the medial amygdaloid nucleus and in the posteromedial cortical amygdaloid nucleus, which are terminals of the neuronal projections from the main and accessory olfactory bulbs, the numbers of Fos-ir cells in those nuclei were not affected by exposure to female-soiled bedding. Moreover, Fos-ir was not detected in the ventromedial hypothalamic nucleus. It is well established that soiled bedding is useful as a source of chemosensory substances, which include "pheromones." Thus, our findings, in agreement with previous behavioral and anatomical data, suggest that the PMv plays a role in initiating male copulative behavior that is induced by a female mice pheromone(s).

Aggression↗
PubMedDate not supplied

Pinealectomy does not affect the entrainment to light nor the generation of the circadian demand-feeding rhythms of rainbow trout.

The pineal organ and its secretory product melatonin are regarded as synchronizers of daily rhythms to the external light/dark (LD) cycle. In fish, the pineal organ acts as a direct photoreceptor, transducing light information into neural and humoral (melatonin) signals. In the present study, we investigate a possible role for the pineal organ and melatonin in the regulation of feeding rhythms of rainbow trout, Oncorhynchus mykiss. We used individual rainbow trout placed in an insulated room at constant temperature (14 degrees C). Fish were self-fed ad lib by means of self-feeders coupled to a computer that continuously recorded demand-feeding activity. Before and after pinealectomy, the fish were exposed to a LD cycle of 16:8 h and then constant light (LL) to test the effect of pinealectomy on demand-feeding rhythms. Feeding records revealed that trout fed exclusively during daytime (96% of feeding confined to the light phase), and that removal of the pineal organ did not disrupt this daily feeding profile, with synchronization to the LD cycle persisting. Moreover, the appearance of circadian feeding rhythms was not affected by pinealectomy: most of the operated fish free-ran with an average tau longer than 24 h. Plasma melatonin rhythms persisted in the pinealectomized trout, but with small amplitude. These results suggest that the pineal may not be the site of the pacemaker that controls feeding rhythms in trout, although further research is required to study the involvement of other photoperiod-transducing systems and melatonin (of nonpineal origin) in the regulation and expression of circadian rhythms in this species.

Animals↗
PubMedDate not supplied

Regulation by guanine nucleotides and cations of melatonin binding sites in the goldfish brain.

Effects of nucleotides and cations on 2-[125I]iodomelatonin binding sites in the goldfish brain were examined. Nucleotides (10(-6)-10(-3) M) dose-dependently inhibited the specific binding with the following order of potency: guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) > GTP = GDP > GMP = ATP > cyclic GMP. Cyclic AMP was ineffective. The treatment of membranes with GTP gamma S induced rapid dissociation of 2-[125I]iodomelatonin from membranes when added at the steady state, increased the Kd and decreased the Bmax values as revealed by saturation analysis, and increased the IC50 value of melatonin to inhibit the specific binding. The treatment decreased the specific binding to membrane preparations obtained from six brain regions as well. Inorganic salts (5-200 mM) dose-dependently inhibited the specific binding with the following order of potency: CaCl2 > MgCl2 > LiCl > NaCl > choline chloride > KCl, except for 5 mM MgCl2, which enhanced the specific binding. Saturation experiments demonstrated that 75 mM CaCl2, 100 mM MgCl2 and 200 mM NaCl increased the Kd and decreased the Bmax while 5 mM MgCl2 increased the Bmax value. These results imply that G protein and physiological concentrations of cations are involved in the regulation of melatonin binding sites in the goldfish brain.

Animals↗
PubMedDate not supplied

Administration of melatonin and related indoles prevents exercise-induced cellular oxidative changes in rats.

In an attempt to define the role of the pineal hormone melatonin and two analogues (5-methoxytryptamine, 5MT, and 6-hydroxymelatonin, 6HM) in limiting oxidative stress, the present study investigated the changes in glutathione, lipid peroxidation, and the activity of the antioxidant enzyme glutathione peroxidase after exercise (swimming for 60 min) with or without treatment with the indolamines mentioned. Lipid peroxidation was measured by estimating tissue levels of malondialdehyde and 4-hydroxyalkenals; the experimental animals in these studies were male Sprague-Dawley rats. In the liver, swimming exercise increased the levels of reduced glutathione (GSH) and also significantly increasing oxidized glutathione (GSSG), while decreasing the GSH/GSSG ratio, an index directly related to oxidative stress. When the animals were treated with melatonin, the concentrations of GSH and GSSG were also increased after swimming; however, no reduction in the GSH/GSSG ratio appeared. In the animals treated with 6HM the changes were the same as in those treated with melatonin. In muscle as well, the concentration of GSH and the GSH/GSSG ratio were decreased following 60 min of swimming. Pretreatment of the rats with melatonin prevented these effects. Pretreatment of the rats with both 5MT and 6HM also prevented the changes. Brain GSH/GSSG ratio was not affected by either exercise or indolamine administration. Swimming enhanced lipid peroxidation in the liver, muscle and brain; however, this was prevented in animals treated with melatonin or 6HM before swimming. Glutathione peroxidase was significantly elevated after exercise in the brain but not in the liver and muscle. It is concluded that swimming imposes a severe oxidative stress and suggests that melatonin and, to a lesser degree, 5MT and 6HM confer protection against the oxidative damage associated with swimming for 60 min. This mechanism may be reasonably attributed to their indole structure, which possibly allows these molecules to act as free-radical scavengers.

5-Methoxytryptamine↗
PubMedDate not supplied

Photic and circadian regulations of melatonin rhythms in fishes.

Photic and circadian regulations of melatonin rhythms in the pineal organ and the retina of several teleosts were studied to investigate the regulatory mechanisms of melatonin rhythms in fishes. In the eyecup preparations of the goldfish, Carassius auratus, both time of day and lighting conditions affected melatonin production, with high melatonin production observed only in the dark-treated group incubated during the 'subjective' night. Thus, in the goldfish retina, local photoreceptors and an ocular circadian clock seem to regulate melatonin production, as in the zebrafish retina and in the pineal organ of a number of teleosts, including the goldfish. However, this circadian regulation of melatonin rhythms is not universal among fishes. Although the superfused pineal organ of the masu salmon Oncorhynchus masou secreted melatonin in a rhythmic fashion under light-dark (LD) cycles, the rhythm disappeared under constant darkness (DD), as in the rainbow trout, with a large amount of melatonin released both during the subjective day and the subjective night. These results suggest that all salmonids lack circadian regulation of melatonin rhythms. Furthermore, when ocular melatonin rhythms were compared in two cyprinids, the ugui Tribolodon hakonensis and the oikawa Zacco platypus occupying different ecological niches, ocular melatonin contents exhibited daily variations, with higher values during the dark phase of LD cycles in both species. The rhythmic changes persisted in the ugui under DD, with higher levels at subjective midnight than at subjective midday; however, ocular melatonin levels in the oikawa were consistently high under DD. Thus, the circadian regulation of melatonin rhythms in fishes is influenced not only by phylogeny, but also by the ecological niches of the animals. These results suggest that the physiological functions of melatonin in the circadian and photoperiodic systems differ among fishes.

Animals↗
PubMedDate not supplied

Antineoplastic effect of orally administered 1-alkyl carbamoyl derivatives of 5-fluorouracil on sc implanted Lewis lung carcinoma and B16 melanoma.

The antitumor activity of 1-alkyl carbamoyl derivatives of 5-fluorouracil against Lewis lung carcinoma and B16 melanoma by long-term oral administration was examined. The 1-hexyl and 1-phenethyl carbamoyl-5-fluorouracil derviatives were markedly active against early Lewis lung carcinoma among the derivatives tested. These compounds were not markedly active against advanced Lewis lung carcinoma but did show acceptable activity. Increases in lifespan in mice with early Lewis lung carcinoma at optimal doses of 1-hexyl and 1-phenethyl carbamoxyl-5-fluorouracil were 98% and 78% respectively. In advanced Lewis lung carcinoma, the 1-hexyl derivative was active by either intermittent or daily administration, but the 1-phenethyl derivative was active only by daily administration. Lung metastases were not inhibited by optimal doses of the 1-hexyl derivative but were completely inhibited by the 1-phenethyl derivative. The 1-hexyl derivative was also active against B16 melanoma and the increase in lifespan at optimal doses was 27%. As a result, 1-hexyl carbamoyl-5-fluorouracil was found to be the most active derivative against early Lewis lung carcinoma and B16 melanoma. However, 1-phenethyl carbamoyl-5-fluorouracil was the most active derivative against advanced Lewis lung carcinoma by daily administration and this compound completely inhibited lung metastases, while 5-fluorouracil and cyclophosphamide did not inhibit lung metastases.

Administration, Oral↗
PubMedDate not supplied

Effects of interleukin-2 and interferon-beta treatment on lymphocytes in various tumor-bearing mice.

Treatment with a combination of recombinant human interleukin-2 (rHIL-2) and recombinant mouse interferon-beta (rIFN-beta) had a significant antitumor effect against subcutaneous (s.c.) adenocarcinoma-755 and colon-38, but this combination performed no better than rHIL-2 alone against s.c. Lewis lung carcinoma in C57BL/6 mice. Injecting a combination of rHIL-2 and rIFN-beta into mice with adenocarcinoma-755 or colon-38 tumors resulted in a marked increase in L3T4+, Lyt-2+ and asialo GM1+ cells in the peritoneal cavity. On the other hand, the treatment of mice with Lewis lung carcinoma with rHIL-2 and rIFN-beta produced almost no change of each subset in the peritoneal cavity compared to cytokine alone. Thus, sensitive tumors (adenocarcinoma-755 and colon-38) in combined treatment with rHIL-2 and rIFN-beta markedly increased L3T4+, Lyt-2+ and asialo GM1+ cells in the peritoneal cavity, but the insensitive tumor (Lewis lung carcinoma) did not.

Adenocarcinoma↗