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Biomedical subjects

S Kai

Publications and source records attributed to S Kai.

At least 73 records · Page 4Linked to original sources
PubMed1992

Effects of mianserin in chronic schizophrenia.

1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. Twenty inpatients with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 5-HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. There were no significant changes in MHPG levels between the two groups. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment.

Adult↗
PubMed1992

[Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats].

In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L-arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).

Animals↗
PubMed1992

[Recurrent pulmonary edema in a patient with acute lymphoblastic leukemia after syngeneic bone marrow transplantation].

Severe respiratory distress appeared in a 14-year-old girl with acute lymphoblastic leukemia 2 months after receiving syngeneic bone marrow transplantation (BMT) with a conditioning regimen of a high-dose of busulfan, etoposide and nimustine. Rapid body-weight gain and edema, especially in eyelids and lower-limbs, were also observed. Without any findings of heart failure nor GVHD, pulmonary edema was recognized on the chest roentgenogram. As soon as the diagnosis of pulmonary edema due to 'capillary leak syndrome' was suspected, the patient was treated with intravenous administration of diuretics, albumin and bolus methylprednisolone in combination of mechanical ventilation. Although the clinical manifestations were improved by the treatment, the disease recurred 5 weeks later. The patient was successfully treated by the same medications, and there has been no recurrence as of the sixth month after discontinuance of the therapy. At present, the mechanism of capillary leak syndrome is still undefined. In this case, however, we speculate that the conditioning regimen for BMT intensified the capillary disturbance initially caused by intensive chemotherapy since remission induction. Furthermore hypoalbuminemia due to severe anorexia might have enhanced the occurrence of the disease.

Adolescent↗
PubMed1992

[Optimal branching of hepatic artery in patients with liver cirrhosis].

Optimality in branching structure of the hepatic arterial vessel in 16 patients with liver cirrhosis was studied. The controls used in this study were 14 patients with gastric or colonic cancer not accompanied by liver dysfunction. Optimality principle was based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Measurements were made of parent and branch vessel diameters from selective celiac arteriogram. After that we measured the included angles of the branch-points of portal vein using ultrasonography. The branch-points of interest were the third bifurcations of right intrahepatic portal vein and artery. The following results are presented in terms of three parameters (r2(2)/r1(2), r1/r0, and r2/r0). The theoretical equations have been shown by several authors. The curve representing these equations was shown by Zamir. We analyzed the scatter of the data points and compare the theoretical and actual results with them. The extent of the scatter is studied making a comparison between control patients and patients with cirrhosis. The data points in control patients were plotted near the theoretical curve. In patients with cirrhosis, the data points show a definite tendency to be plotted far away from the theoretical curve, when we take account of both vessel diameters and branching angles. This discrepancy between theoretical values and actual data in patients with cirrhosis is considered to be caused by the following factors which may influence the vascular structure; hemodynamic change caused by increase of intrahepatic shunt, and morphological change caused by increased fibrosis or/and parenchymal nodules of the liver.

Celiac Artery↗
PubMed1991

Transactivation of the TPA-responsive element by the oncogenic C-erbB-2 protein is partly mediated by protein kinase C.

The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun/Fos-mediated transcriptional activation in nuclei.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Effects of indeloxazine hydrochloride on sleep in normal humans.

The effects of 40 mg of indeloxazine hydrochloride, a cerebral metabolic enhancer, on sleep were investigated in 6 healthy male students. Polygraphic recordings were made for 8 consecutive nights on each subject. An inert placebo was given on the first 3 nights and on the 7th and 8th nights, and 40 mg of indeloxazine was administered on the 4th, 5th and 6th nights. Drug and placebo were administered orally at 21:30 h, and the recording of polysomnograms started at 22:00 h and ended at 8:00 h the next morning. The polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. Indeloxazine prolonged both sleep latency and REM latency, and increased stage 1 sleep, but decreased stages 3, 4 and REM sleep. A significant increase of REM sleep was observed on the 7th and 8th recovery nights. No obvious changes were shown in the subjective assessments after administration of the drug. These results suggest that the effects of indeloxazine on sleep are similar to those of the tricyclic antidepressants. Furthermore, polysomnographic examinations might be useful in evaluating the pharmacological properties of cerebral metabolic enhancers.

Adult↗
PubMed1990

Effects of mianserin on negative symptoms in schizophrenia.

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.

Adult↗
PubMed1990

[Acute toxicity study of buspirone hydrochloride in mice, rats and dogs].

Buspirone hydrochloride (abbr. to BH), an anxiolytic drug, was examined for its intravenous, subcutaneous or oral acute toxicity using Crj: CD-1 (ICR) mice, Crj: CD (Sprague-Dawley) rats and beagle dogs of both sexes. The results obtained were summarized as follows: 1. Drug-related toxic signs included decreased activity and convulsions accompanied with salivation and opisthotonus in mice and rats treated with BH regardless of administration routes, and tremors and clonic convulsions accompanied with salivation in dogs treated with BH orally. 2. Pathological examinations revealed distention of the stomach in dead rats treated with BH orally, and hypersecretion of gastric juice and alterations (viz. edema, necrosis and petechia) on the superficial mucous membrane in the gastropyloric region in dead dogs treated with BH orally. 3. The cause of death was considered to be due to respiratory insufficiency in every species of animals examined. 4. LD50 values (mg/kg) were as follows: [table: see text] 5. No sex differences were observed in every species of animals regardless of administration routes on the basis of toxicological parameters examined.

Administration, Oral↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1990

[Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs].

In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats].

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗