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Biomedical subjects

S Nagase

Publications and source records attributed to S Nagase.

At least 73 records · Page 4Linked to original sources
PubMed1996

Therapeutic significance of the polyamine level in tissues of rats treated with adriamycin and cisplatin.

The effects of adriamycin (Adr) and cisplatin on body weight, organ weight, and the contents of putrescine, spermidine and spermine in 15 different tissues were examined in rats that had been given these drugs for 5 days. The weight of the spleen in cisplatin-treated rats, and of the thymus, spleen, kidney and heart in Adr-treated rats showed statistically significant decreases. Neither Adr nor cisplatin should be used to treat cancers in the seminal vesicle, and Adr should not be used to treat those in the large intestine due to significant increases in spermidine and spermine, which are associated with a risk of re-growth. However, Adr is recommended in the treatment of cancers in the thymus, kidney, skeletal muscle (femoral), heart, prostate, testis, liver, small intestine and lung, based on decreases in some of the polyamines, while cisplatin is not recommended in the thymus, kidney, skeletal muscle or heart for the same reason that Adr is not recommended to treat cancers of the large intestine (rectum). The ratio of spermidine to spermine was significantly higher in the skeletal muscle of cisplatin-treated rats and in the small intestine and brain of Adr-treated rats, and was lower in the prostate, seminal vesicle and spleen of Adr-treated rats than in control rats.

Animals↗
PubMed1996

Polyamine levels in various tissues of rats treated with 3-hydroxy-4-methoxycinnamic acid and 3,4-dimethoxycinnamic acid.

The effects of 3-hydroxy-4-methoxycinnamic acid (3H4MCA) and 3,4-dimethoxycinnamic acid (3,4DMCA) on body weight, organ weight, and the contents of putrescine, spermidine and spermine in 15 different tissues were examined in rats that had been given these compounds for 5 days. In 3H4MCA-treated rats, the weight of the spleen was significantly increased, while none of the other organs showed any significant changes. A diet containing either 3H4MCA or 3,4DMCA should not be taken by patients bearing cancers in the seminal vesicles, spleen or liver, and a diet containing 3,4DMCA should not be taken by patients bearing cancers in the testis, kidney, muscle, small intestine or brain (cortex) because of the significant increases in polyamines, which are associated with a risk of cancer growth, in these tissues. However, a diet containing 3H4MCA is recommended for the management of cancers in the skeletal muscle (femoral), tongue, small intestine (jejunum), stomach, lung and brain based on reductions in polyamines which stimulate tumor growth. A diet containing 3,4DMCA is also recommended for cancer in the prostate, thymus and stomach for the same reason. In addition, a synergic therapeutic effect for the treatment of cancers in these tissues may be anticipated by a combination of such a diet with anti-cancer drugs which reduce polyamine levels. The metastasis of cancers in these tissues may also be inhibited by the reduction of polyamines by these acids. The ratio of spermidine to spermine was significantly higher in the lung of 3H4MCA-treated rats, and lower in the seminal vesicle, thymus, kidney, heart, tongue, stomach and lung of 3,4DMCA-treated rats, than in control rats. The present experiment indicated that cancer patients should pay careful attention to endogenous polyamines in tissues bearing tumors induced by chemicals in ingesta and anti-cancer drugs, in addition to exogenous polyamines.

Animals↗
PubMed1996

Increased lipid peroxidation by rat liver microsomes in experimental renal failure.

This study investigated the peroxidative state of renal failure by measuring lipid peroxidation. The generation of lipid peroxides by rat hepatic microsomes was compared between experimental renal failure caused by 7/8 nephrectomy and healthy control animals. The concentrations of BUN at the point of sacrifice were 84.2 +/- 18.4 (mean +/- SD) in nephrectomized and 19.8 +/- 4.3 mg/dl in the control group (p < 0.01, n = 5). Microsomal generation of thiobarbituric acid reactive substance was 31.2 +/- 2.8 in the nephrectomized group and 20.9 +/- 4.9 nmol/incubation/min in the control group. There was a significant difference between the groups (p < 0.01, n = 5). In summary, the generation rate of lipid peroxides in the microsomes obtained from the rats with experimental renal failure was significantly higher than the control. This study confirms an increased peroxidative state, and specifies one of the sites of increased lipid peroxide generation in renal failure.

Animals↗
PubMed1996

Decreased serum antioxidant activity of hemodialysis patients demonstrated by methylguanidine synthesis and microsomal lipid peroxidation.

This study aims to raise the possibility of methylguanidine, a peroxidative product of creatinine, as a measure of the peroxidative state. As a known standard, we measured the inhibitory effect of uremic serum on the NADPH-dependent microsomal lipid peroxidation. This is an established method for evaluating the peroxidative state and is compared to the effect of uremic serum on methylguanidine synthesis. The study shows decreased serum antioxidant activity in hemodialysis patients by both methods, though there is no correlation between them. These results support the use of methylguanidine as a peroxidative marker and suggest a difference in the reactive oxygen species involved in the reactions of methylguanidine synthesis and microsomal lipid peroxidation.

Adult↗
PubMed1996

Synthesis of guanidinosuccinate from argininosuccinate and reactive oxygen in vitro.

Synthesis of guanidinosuccinic acid (GSA), a uremic toxin, has been suggested to relate to the urea concentration and synthetic rate. Among the urea cycle enzymes, inhibition of argininosuccinate (ASA) lyase by urea has been reported. Argininosuccinate which contains a GSA structure is a candidate of a GSA precursor. We found that another uremic toxin, methylguanidine, is formed from creatinine with reactive oxygen species. Therefore, we investigated in vitro whether GSA is formed from ASA with reactive oxygen species. GSA was measured by HPLC by a post-column-labeling method using 9,10-phenathrequinone. When 1 mmol/l ASA was reacted with the hydroxyl radical-generating system for 5 min at pH 7.4, 9 mumol/l GSA was formed. Dimethylsulfoxide, a hydroxyl radical scavenger, markedly inhibited GSA synthesis. The superoxide radical generated by xanthine and xanthine oxidase reaction also formed 1 mumol/l GSA from 1 mumol/l ASA and the GSA formation was inhibited by superoxide dismutase or catalase almost completely. Addition of FeCl2 to the xanthine/xanthine oxidase reaction further increased GSA synthesis. These results indicate that GSA is formed from ASA by reaction with the hydroxyl radical and the superoxide radical.

Argininosuccinic Acid↗
PubMed1996

Role of reactive oxygen and argininosuccinate in guanidinosuccinate synthesis in isolated rat hepatocytes.

The synthesis of guanidinosuccinic acid (GSA) increases in uremics, and GSA is implicated as a uremic toxin. The GSA synthesis increases roughly in proportion to the serum urea level that increases in patients with renal failure. Urea is a specific inhibitor of argininosuccinase, the fourth urea cycle enzyme, and might lead to the increase of argininosuccinate (ASA). We found that GSA is formed from ASA by reactive oxygen species in vitro. In this paper, we investigated GSA synthesis from ASA in isolated rat hepatocytes and the effect of reactive oxygen species on this synthesis. When isolated rat hepatocytes were incubated with 5 mmol/l ASA, GSA was formed linearly with time up to 6 h (16 nmol/g wet liver/6 h). GSA was formed depending on the ASA concentration up to 10 mmol/l. Dimethylsulfoxide, a hydroxyl radical scavenger, inhibited GSA synthesis by 65%. GSA was actively formed when the hepatocytes were incubated with 32 mmol/l urea. The GSA formation in the presence of urea was also inhibited by dimethylsulfoxide, although the inhibition was less marked. FeCl2, that increases the hydroxyl radical generation, increased GSA synthesis. These results indicate that GSA is formed from ASA in isolated hepatocytes. The results also suggest that reactive oxygen species are important for GSA synthesis in the cells.

Animals↗
PubMed1996

Indications for laparoscopic surgery of ovarian tumors.

To investigate the criteria for laparoscopic surgery in ovarian tumors, a retrospective review of indications, preoperative assessments using transvaginal ultrasonography, serum CA 125, surgical methods and diagnosis and post-operative complications were analyzed. Forty-three patients underwent surgical treatment for ovarian tumors, from November 1992 to October 1993. Of the 43 patients with ovarian tumors, 19 (44%) underwent laparoscopic surgery, and 24 (56%) underwent laparotomy. Laparoscopic surgery was performed in 18 of 34 (53%) patients with benign ovarian cysts. Eight patients with malignant ovarian tumors were treated by laparotomy. Coincidence of preoperative assessment and surgical diagnosis was 95%. No major complications were observed in the laparoscopic surgery. We suggest that malignant ovarian tumors and inextricable adhesions are contraindications to laparoscopic surgery. We propose the following criteria for laparoscopic surgery by classification into three groups: A) good indication: benign cystic tumors with good mobility, B) deliberation indication: benign tumors with poor mobility, including some dermoid cysts and endometrial cysts, C) contraindication: malignant tumors and dense adhesions. We conclude that indications of laparoscopic surgery for ovarian tumors should be determined by careful preoperative assessment using transvaginal ultrasonography and tumor markers.

CA-125 Antigen↗
PubMed1995

Deafness-induced plasticity in the mature central auditory system.

Studies in rats and guinea pigs indicate that local changes in inhibitory transmitters may underlie deafness-induced plastic changes in electrophysiological responsiveness of cells of the mature central auditory system. Following 21 days of bilateral deafness there is an increase in evoked Fos-immunoreactive neurones in the central nucleus of the inferior colliculus (CIC) to contralateral cochlear electrical stimulation, compared with normal or 1-day deafened animals. Deafness is also associated with a dramatic reduction in the population of CIC neurones that respond with suppression of activity to electrical stimulation. Moreover, in vivo microdialysis reveals a marked decrease in gamma-aminobutyric acid (GABA) release from the CIC cells in deafened animals. The results may have general implications for the mediation of central nervous system plasticity induced by deafferentation of sensory input.

Animals↗
PubMed1995

Increasing development of pepsinogen-altered pyloric glands and adenocarcinoma in glandular stomach of analbuminemic rats.

The susceptibility of pepsinogen-altered pyloric glands (PAPG) and neoplastic glandular stomach lesions induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and catechol or sodium cholate in Nagase analbuminemic rats (NAR) was compared to Sprague-Dawley rats (SD). Male NAR and SD rats were given a single dose of 80 mg/kg body weight of MNNG by gastric intubation and, 2 weeks later, fed basal diet containing 0.8% catechol or 0.3% sodium cholate for 18 weeks. The animals were killed at the end of week 20 or after maintenance on basal diet at week 60. The number of pepsinogen-altered pyloric glands at week 20 was significantly (P < 0.001) higher in NAR fed either catechol or sodium cholate compared with SD rats. At week 60, adenomatous hyperplasias and adenocarcinomas were observed in 7 (88%; P < 0.01) and 3 (38%; P < 0.01) of 8 NAR fed catechol and in 4 (22%) and 0 of 18 SD rats, respectively. The results show that the frequency of PAPG in NAR and SD rats is related to the susceptibility to glandular stomach carcinoma. PAPG is a useful endpoint lesion for evaluation of gastric carcinogenicity in a 20-week carcinogenicity test, and NAR are sensitive for glandular stomach carcinogenesis.

Adenocarcinoma↗
PubMed1995

Inhibition of nitric oxide production increases dimethylnitrosamine-induced liver injury in rats.

Intravascular coagulation is involved in the development of certain types of liver injury, including that induced by dimethylnitrosamine. Nitric oxide inhibits platelet aggregation and adhesion; however, its role in protecting against intravascular coagulation has not been clarified. We therefore investigated the effect of blocking the production of NO in a dimethylnitrosamine-induced liver injury model. Wistar male rats received dimethylnitrosamine (50 micrograms/kg) intraperitoneally, and were treated with N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase, or N omega-nitro-D-arginine, an inactive isomer. Each arginine derivative (40 mg/kg) was injected intraperitoneally every 6 h. Twenty-four hours after dimethyl-nitrosamine administration, we observed a significant increase in the serum level of alanine aminotransferase in the N omega-nitro-L-arginine group compared with the N omega-nitro-D-arginine group. The N omega-nitro-L-arginine-treated group also exhibited a significant reduction in platelet count, a prolongation of prothrombin time, and an elevation of plasma soluble fibrin monomer complex levels. Sinusoidal congestion, intravascular coagulation, and coagulation necrosis around the central veins were prominent in the N omega-nitro-L-arginine group. In conclusion, the inhibition of nitric oxide production exacerbated the hepatic damage induced by dimethylnitrosamine, mediated by the acceleration of intravascular coagulation.

Animals↗
PubMed1995

Serum 7 alpha-hydroxycholesterol as a new parameter of liver function in patients with chronic liver diseases.

To examine bile acid synthesis in chronic liver diseases, serum total 7 alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n = 23), patients with chronic hepatitis (n = 21), and control subjects (n = 18). The serum 7 alpha-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 +/- 59 pmol/mL vs. 237 +/- 97 pmol/mL; mean +/- SD). However, in patients with chronic hepatitis, the level was fully retained (262 +/- 102 pmol/mL). Serum 7 alpha-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range. Serum 7 alpha-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities. We conclude that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serum 7 alpha-hydroxycholesterol may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases.

Adult↗
PubMed1995

Anaphylactic reaction to cefazolin in pregnancy.

Anaphylaxis is a rare event in pregnancy, but is one that can have serious implications for both the mother and fetus. We report a case of severe anaphylactic reaction to intravenous (i.v.) cefazolin (CEZ) given during labor with premature rupture of membranes. Maternal shock and prolonged fetal bradycardia occurred. Both the maternal and fetal outcomes were good following treatment with ephedrine, glucocorticoids, and emergency caesarean section.

Adult↗
PubMed1995

Plasmodium vivax malaria infection diagnosed by indirect fluorescent antibody test.

We present the diagnostically challenging case of a 51-year-old Japanese male who visited Papua New Guinea for one month. Approximately a month after returning to Japan, he experienced a high fever. Malaria was suspected and he was admitted to Tsukuba University Hospital. Although the blood smear did not reveal the malarial parasite, a diagnosis of malaria was made using an indirect fluorescent antibody test (IFAT). The patient was treated and discharged but symptoms returned three months later. This time, the blood smear was positive for malarial parasites. IFAT was useful in this case for the early diagnosis of Plasmodium vivax and for ruling out infection by Plasmodium falciparum.

Animals↗
PubMed1994

Subchronic (12-week) inhalation toxicity study of methanol-fueled engine exhaust in rats.

To evaluate the inhalation toxicity to rats of exhaust at low concentration for longer periods, Fischer 344 rats were exposed to 3 concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent increase carboxyhemoglobin in the erythrocytes and decrease in cytochrome P-450 in the lungs were observed in all treated groups. Furthermore, significant increases in plasma formaldehyde were observed in all treated groups. Furthermore, significant increases in plasma formaldehyde were observed in the group exposed to the highest concentration of exhaust (carbon monoxide, 89.8 ppm; formaldehyde, 2.3 ppm; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in any group, and no methanol or formic acid was detected in the plasma in any animals. Histopathologically, exposure-related changes were found only in the nasal cavity of the high-concentration group. Slight hyperplasia/squamous metaplasias of the respiratory epithelium lining the nasoturbinate and maxilloturbinate were observed after 4 wk of exposure, and the incidences and degrees of these lesions increased slightly with the exposure time. No changes were found in the olfactory epithelium of the nasal cavity. As judged by optical microscopy, the exhaust concentration with no effect on the nasal cavity under the experimental conditions was concluded to be the medium concentration level containing 0.55 ppm formaldehyde. In the present study, however, concentration- and time-dependent increase of carboxyhemoglobin in the erythrocytes and decrease of the lung P-450 level were observed. Therefore, further study on more long-term inhalation of lower concentrations of exhaust might be needed.

Administration, Inhalation↗