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Biomedical subjects

H Nagano

Publications and source records attributed to H Nagano.

At least 181 records · Page 10Linked to original sources

Placental transfer of ochratoxin A and its cytotoxic effect on the mouse embryonic brain.

Pregnant ICR mice were given a single ip injection of 5 mg ochratoxin A/kg on day 11 or 13 of pregnancy. Concentrations of ochratoxin A in the maternal serum and tissues reached maximum levels within 2 hr of the injection and then decreased rapidly. The half-life of the toxin in serum was 28.7 hr on day 11 and 23.6 hr on day 13. On the other hand, the concentrations of ochratoxin A in the embryos were very low 2 hr after injection and then gradually increased up to 48 and 30 hr after injection on day 11 and 13, respectively. Pharmacokinetically, the embryo was found to be a 'deep' compartment. In mice treated with ochratoxin A on day 10 of pregnancy, the incidence of pyknotic cells in the telencephalon of the embryos began to increase 12 hr after injection to a peak between 36 and 48 hr, coinciding with the time of peak concentration of the toxin in the embryo.

Amniotic Fluid↗

Vasodilator effects of cepharanthine, a biscoclaurine alkaloid, on cutaneous microcirculation in the rabbit.

Cutaneous microcirculatory responses to intravenous administration of cepharanthine (CT), a biscoclaurine alkaloid, isolated from Stephania cepharantha, were studied in a transparent round chamber installed in a rabbit ear, under conscious conditions. Vital-microscopic observations were made visually with a microscope-closed TV system and microphotoelectric plethysmography. Following the CT administration in doses of 1.0 and 3.0 mg/kg, an enhancement of rhythmic perfusion of microvascular blood due to vasomotion was developed for a period of 1 h or longer, although no appreciable change was observed following CT administration at 10.0 mg/kg. The microvascular dilator effect of CT appeared to have no direct association with systemic hemodynamics, based on the additional measurements of heart rate, blood pressure, carotid blood flow and auricular arterial blood flow.

Alkaloids↗

Relation of regional asynchrony to global left ventricular systolic and diastolic function in patients with angina pectoris without previous myocardial infarction.

To assess left ventricular (LV) systolic and diastolic function globally and regionally and to study the relationship between regional asynchrony and global LV function in patients with stable effort angina pectoris (AP) without previous myocardial infarction, we conducted a resting gated radionuclide ventriculographic study in 15 control subjects (N group) and 22 AP patients with isolated disease of the left anterior descending coronary artery (LAD). In nine of these 22 AP patients, LV systolic and diastolic function before surgical revascularization (Aorto-Coronary Bypass) were compared with those after surgical revascularization. A computer program subdivided the image of the LV into four regions (septal, basal, lateral and apical) by our previously reported method. The time-activity and first-derivative curves of the global LV and three regions (septal, lateral, apical; the basal region was not computed) LV were computed. In the global LV, the peak filling rate (PFR) normalized to LV end-diastolic volume (EDV) and the ratio of increment of filling volume at 100 msec from global end-systole (ES) to the EDV (%EFV), which was correlated with the time constant of LV pressure decay during isovolumic relaxation, decreased (p less than 0.01, p less than 0.001, respectively) and time to PFR (time interval from global ES to PFR) was greater (p less than 0.001) in the AP group than that in the N group. However, in the AP group, the ejection fraction (EF), normalized peak ejection rate (PFR) and %1/3SV, which was defined as the percent stroke volume ejected during the first third of the global LV ejection phase, were not different from these in the N group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Studies on macrocyclic lactone antibiotics. XI. Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues.

The mode of action of rhizoxin (1a), a new antitumor macrolide, was investigated. Rhizoxin inhibited fusion of the male and the female pronuclei in fertilized sea urchin eggs and inhibited cilia formation in the deciliated sea urchin embryos. In vitro, polymerization of tubulin isolated from porcine brains was completely inhibited at a 1 X 10(-5) M concentration of rhizoxin, and tubulin which had been polymerized by incubation at 37 degrees C for 30 minutes was depolymerized by addition of 1 X 10(-5) M of the drug. Activity of rhizoxin against tubulin polymerization was compared with those of other anti-tubulin drugs such as colchicine, vinblastine and ansamitocin P-3. The homologues of rhizoxin, 1b-3b, also inhibited polymerization of the purified microtuble protein at almost the same extent as rhizoxin.

Animals↗

[Effects of intravenous feeding on adjuvant chemotherapy--an experimental study on the distribution of 5-FU after injection of tegafur (1)].

Forty-eight male Donryu rats inoculated with Sato lung cancer were used to experimentally determine the effects of intravenous feeding on the concentrations of the chemotherapeutic agents FT-207 and 5-FU in the blood, as well as in the liver and tumorigenic tissue. Following FT-207 administration, the blood, tumor and liver tissue levels were lower than in the IVH group (oral administration). The liver 5-FU concentration, at 0.10 +/- 0.02 microgram/g, was significantly higher in the intravenous feeding group than in the p.o. group (0.05 +/- 0.01 micrograms/g). The 5-FU blood concentration rose quickly, reaching 0.051 +/- 0.013 micrograms/ml and 0.035 +/- 0.004 micrograms/ml at 9 and 12 hours, respectively, following treatment. This was significantly higher than in the p.o. group, which showed corresponding levels of 0.031 +/- 0.004 microgram/ml and 0.022 +/- 0.002 microgram/ml, respectively. The increase in the 5-FU level within the tumor was markedly high in the IVH group compared to the p.o. group, and it peaked at 9 hours following administration. The concentration in the IVH group was thus higher than in the p.o. group at any given time. At 24 hours after treatment, the IVH group level was 0.35 +/- 0.09 microgram/g, against 0.27 +/- 0.05 microgram/g in the p.o. group. The blood concentration of 5-FU following intravenous feeding maintained a high value for a long time, and the 5-FU tumor concentration also remained at a high level. The intravenous route was therefore considered to be advantageous for antitumor chemotherapy.

Animals↗

[Serum concentration of 5-FU and tegafur (FT-207) after administration of tegafur (FT-207) suppository with the colostomy].

Tegafur (FT-207) suppositories were administered at a rate of 750 mg via the artificial anus (ST Group) following surgery of rectal cancer. Comparative studies were conducted of changes in blood concentrations of 5-FU and tegafur at the time of initial administration and following one week of continuous use for the low-anterior resection cases (LA Group) and the rectal administration cases (RE Group). FT-207 concentration at initial administration was low in the ST group compared to those for both LA and RE groups which received anal administration of the drug, but only little changes were noted. Blood concentration one hour after administration was 11.1 micrograms/ml, elevated to 14.3 micrograms/ml at two hours, and remained at 10 micrograms/ml and above for six hours following administration. The ST group 5-FU concentrations at two, four and six hours after administration were significantly lower than those in the RE group but the changes were little. Blood concentrations were 0.015 microgram/ml at one hour after administration, 0.017 micrograms/ml at two hours and maintained virtually the same level thereafter. An effective concentration of 0.012 microgram/ml was maintained even at ten hours following administration. After one week of administration of the suppositories, the ST group showed the lowest concentration among three groups, but it was approximately double compared to the initial concentration; FT-207 showed nearly the same concentration in the LA group and 5-FU blood concentration was 0.025 microgram/ml at one hour after administration, reached to a maximum of 0.030 microgram/ml at two hours and maintained 0.020 microgram/ml and higher at ten hours. 5-FU concentration in the LA and RE groups after one week of continuous administration showed a dual-peaked pattern. No patient with an abnormal artificial anus was involved in this study. The artificial anus is thought to be an adequate and effective administration route of FT-207 suppositories.

Adult↗

[Effects of intravenous alimentation on adjuvant chemotherapy--an experimental study on the distribution of 5-FU after injection of tegafur (2)].

The stomach, small and large intestines, heart, lungs, bone and kidneys were removed from 48 Sato lung cancer-bearing rats used in the previous experiments and given 90 mg/kg of tegafur (FT-207) by single intravenous administration and tissue 5-FU and FT-207 concentrations were measured. FT-207 concentration in the alimentary canal was somewhat lower than the blood concentration, but both were lowered in parallel. 5-FU concentration in the stomach and large intestines showed virtually identical changes in both IVH and PO groups, but IVH group tended to have higher concentration. IVH group showed higher values than PO group anytime, particularly in the large intestines. A reduction of the side effects on the digestive system via intravenous alimentation was thought due to the elimination of mechanical stimulation via a cessation of oral feeding. 5-FU concentration in the bone was highest in PO group at six hours after administration and blood concentration changes were parallel, but there was virtually no change in IVH group. Maximum values were found one hour after administration and slowly declined thereafter; at 24 hrs the values were 0.059 +/- 0.013 microgram/g, relatively high compared to the PO group at 0.041 +/- 0.022 microgram/g. In the present study under intravenous alimentation, the concentration changes were slight in spite of 5-FU maximum concentration being lower than that by oral feeding and the long-term high concentration which was maintained; this is thought to be a disadvantageous action with regard to the bone marrow. FT-207 concentration in the kidney, heart and lungs was the same as that for the blood, with a gradual reduction in IVH group. 5-FU concentration was the same for the kidneys and IVH group quickly reached to the high levels compared to PO group with only slight changes thereafter. Effects of continuous water load might be involved but not clear.

Animals↗

[Clinical trial of forphenicinol for the lung infection with Mycobacterium avium, Mycobacterium intracellulare complex].

Clinical evaluation of forphenicinol, a low molecular weight immunomodulator, in patients with Mycobacterium avium, Mycobacterium intracellulare complex pulmonary infections has been conducted in a multicenter trial participated by 9 institutions in Kyushu during a period of 12 months from July 1982 to August 1983. Forphenicinol was administered for 6 months without changing the regimen of antituberculous drugs used previously. The following results were obtained. 1. Ten out of 33 eligible patients were evaluated as showing good responses; In 5 of them, elimination of M. avium, M. intracellulare complex from sputum was observed. In the other 5 patients, number of bacilli excreted was decreased significantly after treatment. 2. All of the cases with good responses were those which were simultaneously administered with antituberculous drugs. 3. Patients with thick-walled cavities, following cured tuberculosis, which was superimposed with M. avium, M. intracellulare complex, were poorly responded to forphenicinol. 4. Side effects were observed in 3 out of 41 patients; 1 case each with fever, abdominal distension and anorexia. No abnormalities in laboratory test values were observed.

Adult↗