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Biomedical subjects

H Nishi

Publications and source records attributed to H Nishi.

At least 127 records · Page 7Linked to original sources

[Laboratory and clinical investigations of cefodizime in infectious diseases in childhood].

In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients. The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood. We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria. No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.

Age Factors↗

Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro.

Using cultured bovine aortic endothelial cells, the effects of MCI-186, a radical scavenger, were studied on arachidonic acid metabolism and on the cell injury caused by 15-HPETE. MCI-186 at 3 X 10(-5) M enhanced prostacyclin production in the intact endothelial cells without affecting phospholipase A2. When endothelial cell homogenates were used as an enzyme source, it was found that MCI-186 stimulated the conversion of arachidonic acid to prostacyclin like phenol, perhaps by trapping OH radicals produced in the process of the conversion of PGG2 to PGH2. On the other hand, MCI-186 was found to inhibit lipoxygenase metabolism of arachidonic acid in cell free homogenates of rat basophilic leukemia cells. The lipoxygenase inhibition caused by 3 X 10(-5) M MCI-186 was almost equivalent to that caused by 3 X 10(-6) M BW 755C. MCI-186 remarkably protected against endothelial cell damage caused by 15-HPETE. 3 X 10(-5) M of 15-HPETE caused endothelial cell death in about 60% of the population: however, pretreatment of the cells with 10(-5) M of MCI-186 or concomitant addition of 10(-5) M of MCI-186 with 15-HPETE to the cultures prevented the cell death completely. These results suggest that MCI-186 may become an unique anti-ischemic drug.

Animals↗

[Experiences with sultamicillin granules in pediatric patients].

Sultamicillin (SBTPC) is a combination drug of sulbactam (SBT) and ampicillin (ABPC) in an ester bonding at 1:1 ratio. SBT, a new semisynthetic beta-lactamase inhibitor restores and extends the spectrum of ABPC against resistant strains of bacteria. SBTPC granules were administered to 26 pediatric patients with infections, and clinical efficacies were studied in 23 patients. The clinical efficacy rate was 95.7% and the drug was evaluated to be highly effective for the treatment of infectious diseases in the pediatric field. SBTPC was safe and well tolerated.

Age Factors↗

[Effects of intravenous and intracerebroventricular terazosin, prazosin and clonidine on spontaneous sympathetic outflow in rats].

The hypotensive activity of terazosin has been attributed to inhibition of postsynaptic alpha-1 adrenoceptors. The present study examined the influence of terazosin on spontaneous sympathetic outflow in anesthetize and immobilized rats. The effects on blood pressure and heart rate were also evaluated. Intravenously (i.v.) injected terazosin 0.3 mg/kg and prazosin 0.1 mg/kg increased a sympathetic outflow by 15.4 and 21.6%, respectively. These drugs produced a significant and long-lasting fall in blood pressure with slight heart rate change. On the contrary, clonidine 0.1 mg/kg, i.v. significantly inhibited the sympathetic outflow by 69.2%. The intracerebroventricularly administered 10 micrograms/kg clonidine also showed the sympathoinhibitory effect. However 3 micrograms/kg, i.c.v. of terazosin and prazosin increased the sympathetic tone by 16 and 7.2%. During these periods, in both drugs slightly decreased the blood pressure. These changes in hemodynamic parameters and nerve activities were obtained at 2 approximately 3 min after the i.c.v. administration. The 10 micrograms/kg, i.c.v. of terazosin and prazosin significantly inhibited the pressor response by phenylephrine 1 micrograms/kg, i.v. These results indicate the peripheral effect of terazosin and prazosin through the penetration of the drugs from the brain. The results provide evidence that terazosin, like prazosin, dose not affect cardiovascular regulation by a central action.

Adrenergic alpha-Antagonists↗

[Pharmacokinetic and clinical studies on flomoxef in the pediatric field].

The new antibiotic flomoxef (FMOX, 6315-S) was administered to 38 children. The results obtained are summarized as follows. 1. In 3 cases of children administered with FMOX (20 mg/kg) by intravenous drip infusion for 30 minutes, the mean T1/2 (beta) was 0.96 hour and the mean 6-hour urinary excretion was 95.5%. 2. The antibiotic was administered to a total of 38 patients with bronchopneumonia, lacunar tonsillitis, upper respiratory tract infection complicated with brain tumor, otitis media, urinary tract infection, purulent meningitis, subcutaneous and hyponychial abscess, cervical lymphadenitis, or bacterial enteritis. The treatment was markedly effective in 24 cases, effective in 13, fair in 1, and ineffective in none. The efficacy rate was 97.4%. From our results, this drug appears to be particularly effective to bronchopneumonia, upper respiratory tract infection and urinary tract infection. 3. None of the children showed clinical symptoms indicating side effects of the drug. These results showed that FMOX is a drug that can be safely used in the pediatric field as well as for adults.

Age Factors↗

[Basic evaluation of measurement of the serum level of squamous cell carcinoma-related antigen (SCC) and its value following irradiation of cancer of the uterine cervix].

The measurement of the serum level of squamous cell carcinoma-related antigen (SCC) purified from liver metastasis of cancer of the uterine cervix by an RIA kit is basically evaluated. The results of sensitivity, the recovery test, dilution test and variance test are good enough for clinical application. In gynecological disorders, the positive rate is high (62% [29/47]) in patients with cancer of the uterine cervix. Furthermore, the rate and level are related with the clinical staging. The changes of the serum SCC level in irradiated patients with cancer of the uterine cervix were a good reflection of the effectiveness of the treatment.

Antigens, Neoplasm↗

[Cardiovascular effects of MY-5116 and MY-1250].

The effects of MY-5116, isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylate, an anti-allergic drug, and MY-1250, an active metabolite of MY-5116, on the cardiovascular system were studied in dogs, rats and guinea pigs. Orally administered MY-5116 (300 mg/kg) had no effect on the cardiovascular system in anesthetized dogs and conscious rats. In anesthetized dogs, MY-1250 and disodium cromoglycate (DSCG) caused hypotension, bradycardia and reduction of respiration rate from the doses of 3 and 10 micrograms/kg, i.v., respectively. Both drugs showed a tachyphylaxic phenomena which was crossed with each other. MY-1250-induced cardiovascular effects were abolished by bilateral vagotomy. MY-1250 (3-30 micrograms/kg, i.v.) caused a decrease of carotid blood flow, a transient decrease followed by a slight increase of renal blood flow, and a transient increase followed by a slight decrease of femoral blood flow in anesthetized dogs. MY-1250 had no effect on sympathetic ganglion, but increased the contractile force of isolated left atria from guinea pigs at 10(-5) g/ml and increased its rate at 10(-4) g/ml. These positive inotropic and chronotropic effects were not influenced by reserpinization. MY-1250 had no effect on the norepinephrine-induced dose-response curve in isolated rat aorta.

Animals↗

Exercise parameters for the prediction of post-training increase in exercise tolerance in patient with stable angina pectoris.

Twenty cases with effort angina underwent exercise training for a mean follow-up period of 38 weeks. Various parameters were investigated to clarify whether or not such parameters can be used to predict an increase in exercise tolerance of patients with effort angina. The increase of exercise tolerance after training was found to be related to a reduction of the myocardial oxygen demand at a given external work load. The maximal heart rate (max HR) the maximal systolic blood pressure (max SBP) and the maximal rate-pressure product (max RPP) could not predict the post-training increase in exercise tolerance. Before training, the maximal oxygen intake (VO2max) was found to be lower, and the HR/VO2max and the SBP/VO2max were higher in the group (11 patients) which showed a good response to the exercise program (effective group) than those in the group (9 patients) which did not (unchanged group). Before training, the HR/VO2max and the SBP/VO2max in the effective group were also higher than those of 96 healthy adults. On the other hand, the HR/VO2max and the SBP/VO2max in the unchanged group were not different from those of the healthy adults throughout the training. It is useful to compare the values of the HR/VO2max and the SBP/VO2max of patients with effort angina to those of healthy adults for the prediction of post-training increase in exercise tolerance.

Angina Pectoris↗

[Effect of suloctidil in the protection of the cerebral function].

It has been demonstrated that suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] has a protective effect against cerebral hypoxia to elongate the survival time of mice subjected to normobaric hypoxia (96% N2 + 4% O2 gas mixture). In this study, further experiments were done to elucidate the mechanism of protection against cerebral hypoxia with a variety of experimental models. Pretreatment (30 min) with suloctidil (12.5-50 mg/kg, i.p.) increased the number of gasping in the decapitated head of mouse as a complete ischemic model. Pyrithioxine (25, 50 mg/kg, i.p.) or cinnarizine (50, 100 mg/kg, i.p.) did not increase the gasping number. In the histotoxic anoxia with KCN (4 mg/kg, i.v.) in mice, suloctidil showed 30.8% and 46.2% survival rates at the doses of 25 and 50 mg/kg, i.p., respectively. Concerning this result, it has been revealed that suloctidil did not have any methemoglobin formation liability in rats (unpublished). Pyrithioxine did not show such protection following the injection of 12.5-50 mg/kg, i.p.. Suloctidil (3.0-50 mg/kg, i.p.) and pyrithioxine (3.0, 10 mg/kg, i.p.) significantly prolonged the survival time of mice subjected to hypobaric hypoxia (210 mmHg). In this cerebral hypoxia model, suloctidil kept glucose at a significantly higher level and lactate at a lower level in the brain of mice that were administered this drug than the control group. ATP was kept at higher level after suloctidil than the control under hypobaric hypoxia. Taking these evidences together, it can be concluded that suloctidil exerts its cerebral anti-hypoxic effect through cerebral glucose metabolism coupled with oxidative phosphorylation to yield the high energy substance ATP in a variety of models tested in this study. The fact obtained in this study, together with increase in cerebral blood flow by suloctidil, may also elucidate the protective effect of suloctidil against cerebral hypoxia.

Animals↗

[Effects of suloctidil on the central and peripheral nervous systems].

The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.

Analgesics↗

[Effect of suloctidil on the reduced evoked potentials in brain slices in low glucose perfusate].

Effects of suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] on reduced evoked potentials in low glucose perfusate were studied using guinea-pig prepyriform cortex in vitro. The amplitude of evoked potential to paired electrical stimulation of the olfactory tract in cerebral slices was consistently and reversibly suppressed by the perfusion with low glucose (3 mM)-Krebs-Ringer's solution. The amplitude reduction after 10 min exposure to the perfusate was fairly reproducible in the same preparation. The amplitude reduction was always accompanied with significant facilitation of "postactivation potentiation", estimated from the size of the first and second response to paired stimulation. Perfusion of brain slices with low glucose Krebs-Ringer's solution containing 10(-7)-10(-6) g/ml suloctidil for 10 min, however, effectively prevented the reduction of amplitude of evoked potentials to below 30-50% of the control value. The facilitation of postactivation potentiation under the low glucose condition was also suppressed by the drug. Dihydroergotoxin, 3 X 10(-6) g/ml, also showed a comparable effect as 10(-6) g/ml suloctidil. These data suggest that suloctidil possesses a brain energy economizing effect such as activation of oxygen, glucose uptake or production of high energy substance.

Animals↗

[UFT concentration in various tissues from cancer patients].

UFT, an antitumor drug combined of Tegafur 1 and Uracil 4, was administered preoperatively to 23 cancer patients including 11 cases of breast, 8 of gastric, 2 of colon and 2 of other cancers. Tissue specimens of different sites and serum samples were collected during the operation: cancer tissues, normal breast, normal gastric, colon or rectal wall, lymph nodes and subcutaneous fatty tissues, etc., and concentrations of tegafur (FT), 5-fluorouracil (5-FU) and uracil were studied using HCLP or GC-MF methods. In most cases, 5-FU and uracil concentrations detected in cancer tissues from the patients were higher than those found in non cancer sites. FT and 5-FU fractions in cancer tissues were found to be higher than those of the patients receiving only 800 mg of Tegafur fine granules as previously reported. Patients with benign tumor having mastopathy or were reported to show very low 5-FU concentration in tissue which was almost undetectable. From the above results, it has been suggested that UFT is a useful drug in cancer chemotherapy.

Administration, Oral↗

Separation of cytochromes c by reversed-phase high-performance liquid chromatography.

Six kinds of cytochrome c of different origin, i.e., bovine, chicken, dog, horse, rabbit and tuna, were subjected to separation by reversed-phase high-performance liquid chromatography on three commercial packing materials; octadecyl-, octyl- and cyanoalkyl-silicas. The effects of reversed-phase material, mobile phase and temperature on the separation of cytochromes c were examined. The parameters of the mobile phase were the organic modifier, the pH, the salt concentration and additives. Under optimal conditions, five of the six cytochromes c were resolved in 10 min. The relative retention values cannot be explained in terms of the relative lipophilicities of the side-chains of the amino acid residues.

Animals↗

Effects of monoamines injected into the hippocampus on hippocampal seizure discharges in the rabbit.

The effects of intrahippocampally administered catechol- and indoleamines on the two types of hippocampal seizure discharges elicited by electrical and chemical stimulation were examined in unanesthetized rabbits. The catecholamines norepinephrine (NE) and dopamine (DA), injected into the hippocampus in doses of 100--200 micrograms, inhibited electrically induced hippocampal seizure discharges with a 50% increase in the stimulation threshold. However 5-hydroxytryptamine (5-HT) at doses of 50 micrograms to 100 micrograms caused no effect on electrically induced seizure discharges. On the contrary, 5-HT and 5-hydroxytryptophan (5-HTP) at a dose of 50 micrograms potentiated carbachol (5 micrograms)-induced hippocampal seizure discharges, prolonging the duration of seizure discharge three times the control. NE and DA had no effect on this chemically induced hippocampal discharges. It is therefore suggested that the effects of monoamines on hippocampal seizure discharges are very much dependent on the type of stimulation employed for the induction of this phenomenon.

Animals↗