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Biomedical subjects

N Morisaki

Publications and source records attributed to N Morisaki.

At least 163 records · Page 9Linked to original sources

Abnormal metabolism of polyunsaturated fatty acids and phospholipids in diabetic glomeruli.

Studies were done on changes in phospholipid content and fatty acid composition of phospholipids and on the role of the acylation pathway in synthesis of phospholipids in the development of abnormal fatty acid composition in the glomeruli of rats 2 and 10 mo after induction of diabetes with streptozotocin. The proportions of individual phospholipids in the glomeruli of rats were not changed 2 mo after induction of diabetes, but the proportion of phosphatidylethanolamine (PE) decreased and that of sphingomyelin increased 10 mo after induction of diabetes. In contrast, in liver the proportion of PE was increased and that of phosphatidylcholine was decreased. These results showed that changes of individual phospholipids in glomeruli were time-dependent and tissue-specific. Two mo after induction of diabetes, the main change in the phospholipid fatty acid composition of diabetic glomeruli was a decrease in arachidonic acid (AA); the main change in serum free fatty acids (FFA) was an increase in linoleic acid (LA) and a decrease in AA. Ten mo after induction of diabetes, the main changes in the phospholipid fatty acid composition of glomeruli were an increase in LA and a decrease in AA; the main change of the serum FFA composition was a decrease in AA. Thus, the fatty acid composition of glomerular phospholipids was not directly correlated to that of the serum in diabetic rats. Acyl-CoA synthetase and acyltransferase activities increased in diabetic glomeruli with either AA or LA as substrate, but activity toward LA increased more at 2 mo after induction of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibitory effect of FO-1561 (S-adenosyl-L-methionine sulfate tosylate) on phospholipase A2.

The mechanism of the protective effect of FO-1561 (S-adenosyl-L-methionine sulfate tosylate) on mitochondria was investigated using rat heart muscle. FO-1561 stimulated CO2 production from palmitic acid in the mitochondria, indicating an increase in energy production. FO-1561 inhibited mitochondrial swelling induced by Ca2+ added exogenously or by addition of snake venom phospholipase A2. Moreover, FO-1561 inhibited phospholipase A2 activity directly. These results suggested that FO-1561 blocked mitochondrial swelling by inhibiting endogenous phospholipase A2 activity and so preventing decrease in palmitic acid oxidation.

Animals↗

[Effects of cefotetan on PIVKA-II changes in the treatment of infections and prophylaxis of surgical infections in the fields of obstetrics and gynecology].

Cephem antibiotics possessing 1-methyl-1-H-tetrazole-5-yl-thiomethyl moiety at the 3 position of beta-lactam skeleton are known to play a significant role in the disturbance of coagulation and bleeding caused by the deficiency of vitamin K-dependent clotting factors. Among those factors, abnormal prothrombin, protein specifically induced by vitamin K absence or antagonist (PIVKA-II), is recognized to be important. Cefotetan (CTT) is a cephem antibiotic with the above mentioned side chain at the 3 position. In the study reported here, CTT was administered to patients in the fields of obstetrics and gynecology for the treatment of infections (5 patients) and prophylaxis of surgical infections (142 patients). Changes in PIVKA-II levels, hematological and biochemical profiles, and the adverse effects are investigated during the cefotetan treatment. 1. Changes in PIVKA-II levels were observed in 1.2% (1 out of 81) of the patients prior to the CTT treatment and 7.4% (6 out of 81) of patients on the 14th day after the initiation of CTT treatment. 2. Although 6.8% (8 out of 117) of the patients showed slight diarrhoea on day-2 to day-5 after the initiation of CTT treatment, no patients showed any bleeding episodes or adverse effects such as abnormality of biochemical test values and physical signs after the completion of the CTT treatment.

Adult↗

Cytotoxic effects of paraquat and inhibition of them by vitamin E.

Paraquat causes failure of multiple organs including the liver in humans. The kinetics and mechanism of paraquat intoxication were studied using cultured rat hepatocytes. Paraquat induced time- and dose-dependent lactate dehydrogenase release, lipid peroxidation, and cell death, estimated as decrease in protein in cells attached to culture dishes. However, the increase in lipid peroxidation occurred after lactate dehydrogenase release had reached a plateau. Vitamin E inhibited the inductions of all these cytotoxic effects of paraquat. Kinetic studies showed that lipid peroxidation was a better indicator of cell death than lactate dehydrogenase release, because vitamin E inhibited the induction of cell death even when added 6 h after paraquat, when lactate dehydrogenase release had reached a plateau but lipid peroxidation had not. The present results strongly suggest that paraquat exerts its cytotoxicity by a mechanism involving oxidation reactions.

Animals↗

Inhibitory effect of prostaglandin E2 on cholesterol ester accumulation in macrophages.

The effects of prostaglandin E2 (PGE2) on the metabolism of beta-migrating very low density lipoprotein (beta-VLDL) in rat peritoneal macrophages were investigated. When cultured in vitro, macrophages apparently incorporated labelled beta-VLDL time-dependently until 12 h, when the incorporation appeared to reach a plateau. Labelled cholesterol ester in the macrophages increased rapidly until 2 h of incubation, did not change from 2 to 6 h, and then increased markedly until 28 h. Labelled free cholesterol in the macrophages increased until 12 h and then decreased until 28 h. Exogenously added PGE2 (10(-7) approximately 10(-5) M) inhibited the accumulation of labelled cholesterol ester between 6h and 28h with or without increasing the level of labelled free cholesterol. These results suggest that PGE2 prevented cholesterol ester accumulation by stimulating either hydrolysis of cholesterol ester or excretion of free cholesterol.

Animals↗

Fatty acid specificity of acyl-CoA synthetase in rat glomeruli.

The fatty acid specificity of acyl-CoA synthetase in rat glomeruli for physiologically and pathologically important long-chain fatty acids was studied. The apparent Michaelis constants (Km) for substrate fatty acids increased in the order, linolenic less than linoleic less than eicosapentaenoic less than arachidonic less than oleic less than palmitic acid. The maximum velocities with these fatty acids decreased in the order, oleic greater than linoleic greater than palmitic (approximately equal to) linolenic greater than arachidonic greater than eicosapentaenoic acid. The syntheses of radioactive arachidonyl-CoA and palmitoyl-CoA from radioactive arachidonic and palmitic acid, respectively, were both inhibited by all fatty acids mentioned above including the substrate fatty acids, their inhibitory effects being inversely correlated with their apparent Km values. These results suggest that the enzyme in glomeruli has a unique specificity for fatty acids and that there is no arachidonic acid-specific acyl-CoA synthetase in glomeruli. The possible contribution of the glomerular enzyme with this specificity to the abnormal fatty acid levels in diabetic animals is discussed.

Acyl Coenzyme A↗

[Clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

The penetration of imipenem/cilastatin sodium (MK-0787/MK-0791) into tissues of 6 patients and clinical efficacy in 21 patients with infectious diseases were studied in the field of obstetrics and gynecology. The results are summarized below. The transfer of MK-0787/MK-0791 into genital organ tissues was very good. The clinical efficacy was evaluated for 11 patients with intrauterine infections, 5 patients with intrapelvic infections and 5 patients with other infections. Clinical responses were excellent in 7 (33.3%), good in 13 (61.9%) and poor in 1 patient (4.8%), and the efficacy rate was 95.2 percent. Infective bacteria were eradicated in 4, diminished in 2, unchanged in 1 and replaced by other bacteria in 2 patients. No side effect was observed.

Adult↗

[Prophylactic and therapeutic use of cefotetan, a cephem antibiotic, for infections in the field of obstetrics and gynecology].

This paper deals with results obtained from the cefotetan (CTT, Yamatetan) study group of department of obstetrics and gynecology in Yamagata prefecture. Efficacy of CTT, a new cephamycin antibiotic, was studied in 50 cases (39 cases of prophylactic use for postoperative infections and 11 cases of several different infections). CTT was administered to each of the patients at a daily dose of 2 grams. No other drugs such as antimicrobial agents, steroids and antiinflammatory drugs which might affect the efficacy of CTT were permitted during the study except for the drug therapy or surgical procedures required for treating underlying diseases. Fever index, one of the examination items to assess the prophylactic effect for postoperative infections as well as daily changes in maximum body temperature, was examined in the prophylactic group. Daily changes in febrile pattern were examined in the infection group. The fever index were 3.4 +/- 4.0 degree hours in cases subjected to cesarean sections in the prophylactic group, 3.7 +/- 3.0 degree hours in cases subjected to gynecological operations in the prophylactic group and 4.5 +/- 5.5 degree hours in the infection group. The clinical efficacy rate in the 11 cases of the infection group was 100%; excellent in 3 cases and good in 8 cases. Bacteriological examination was conducted in 3 of the 11 cases and bacteria were eliminated in all 3 cases. The overall clinical efficacy rate was also 100%; excellent in 5 cases and good in 6 cases. No abnormal laboratory findings nor side effects were observed in any of the cases.

Adult↗

[The effect of cefotiam in the prophylaxis of postoperative infections in common gynecological surgeries].

Cefotiam (CTM) was administered to 37 cases of cesarean section and 29 cases of total abdominal hysterectomy for prophylactic purposes. Group I was given the agent at a total dose of 14 g (postoperatively 4, 4, 2, 2 and 2 g), group II at a total dose of 10 g (postoperatively 2, 2, 2, 2 and 2 g) and group III at a total dose of 10 g (2 g during operation and postoperatively 2, 2, 2 and 2 g). When fever indices between the groups were compared, group III showed the lowest level of fever index regardless the type of operation. When the results of laboratory test (WBC, CRP, ESR) between the groups were compared, no significant differences were observed, but group III tended to show lower values than others. No side effects due to CTM were noted. The above results indicate that the administration of CTM during operation was the most effective for protection against postoperative infections in terms of changes in fever index and laboratory test values.

Adult↗

[A study of cephem antibiotics, cefazolin and ceftizoxime, for prophylaxis against infections following obstetric and gynecologic procedures].

Cefazolin (CEZ) and ceftizoxime (CZX) were administered prophylactically to prevent postoperative infections after cesarean section and abdominal simple panhysterectomy, common obstetrical/gynecological procedures. The results were summarized as follows. Total fever indices in cesarean sections for the 2 drug groups were examined and CEZ (n = 8) and CZX (n = 10) indices were found to be 6.0 +/- 3.67 degree hours and 3.6 +/- 1.16 degree hours, respectively. In abdominal simple panhysterectomies, CEZ (n = 11) and CZX (n = 11) indices were 8.15 +/- 5.17 degree hours and 4.26 +/- 2.24 degree hours, respectively. Further, there was a lower daily fever index with CZX than with CEZ in both operation groups. Counts of WBC in both procedure groups were lowest on the 5th postoperative day in the CZX group, so was for the CRP. As for the ESR, the CEZ group was much higher than the CZX group especially in abdominal simple panhysterectomies. Neither subjective/objective side effects nor abnormal laboratory findings were observed in either CEZ or CZX group of patients.

Adult↗

[Clinical studies of cefoperazone in the field of obstetrics and gynecology].

Clinical studies of cefoperazone (CPZ) were performed in 65 patients of obstetrics and gynecology, and the following results were obtained. When comparing the fever index of cases treated by CPZ to those by another prophylactic antibiotics, CPZ showed the lowest level comparable to CMX and LMOX. Clinical effects: The effectiveness of CPZ was 75% (excellent in 3 cases, good in 3 cases, poor in 2 cases) in 8 infectious cases. No side effects due to CPZ were noted.

Bacterial Infections↗

[Bacteriological and clinical studies of premature rupture of the membranes].

Cases of premature rupture of the membranes (PROM) were subjected to bacteriological examination of lower genital organs and their clinical courses were analyzed. The results obtained were summarized below. From lower genital organs of cases examined at the 24th-36th week of pregnancy, Gram-positive or Gram-negative aerobes were detected at a high rate in both the group without PROM (-) and the group with PROM (+). From patients in the group with PROM + chorioamnionitis (CAM) anaerobes as well as aerobes were detected at especially high rates. Many patients with PROM (+CAM) were administered with penicillin-antibiotics orally or parenterally. Clinical analysis showed effectiveness of these antibiotics which were especially effective when administered intravenously. The oral administration produced inferior results to the injection judging from clinical results. Patients with PROM and infection during the puerperal period were examined. They were found to include 15 cases of intrauterine infection and 6 cases of puerperal fever. Patients who started showing infectious symptoms at a later time than 8 hours after the onset of PROM tended to have a higher frequencies of infections. The rate of occurrence of cases requiring cesarean section was higher in this group than in the group where infectious symptoms started within 8 hours after PROM.

Cervix Uteri↗

Fatty acid metabolism and cell proliferation. VII. Antioxidant effects of tocopherols and their quinones.

The antioxidant capacities of alpha- and gamma-tocopherols (alpha-E and gamma-E) and their quinones (alpha-EQ and gamma-EQ) were determined in non-biological and biological systems. The non-biological system consisted of arachidonic acid [20:4 (n-6)], the oxidant cumene hydroperoxide, and a Fe3+ catalyst to facilitate malondialdehyde (MDA) formation from lipid peroxides. alpha-E and gamma-E had similar antioxidant capacities in this system. alpha-EQ also functioned as an antioxidant, while gamma-EQ exhibited a crossover effect by functioning as an antioxidant at low concentrations and a prooxidant at high concentrations. Biological lipid peroxidation in smooth muscle cells challenged with 20:4 (n-6) was measured both by MDA formation in confluent cultures and by cell growth in proliferating cultures. alpha-E, gamma-E and alpha-EQ had similar antioxidant capacities, but gamma-EQ was highly cytotoxic for cells in both confluent and proliferating cultures. Cellular retention of antioxidants was estimated indirectly from MDA formation when cells were loaded with an antioxidant (preincubation) and then incubated for varying periods of time in fresh media containing 20:4 (n-6). Cellular retention also was measured directly with tritiated alpha-E and tritiated alpha-EQ. These studies showed that cellular retention decreased in the sequence gamma-E greater than alpha-E greater than alpha-EQ. Thus, cellular retention does not explain the enhanced antioxidant capacity of alpha-E compared to gamma-E that has been reported for animal systems. The antioxidant capacity of alpha-E evidently is enhanced by its metabolism to a quinone which, unlike the quinone from gamma-E, functions as a biological antioxidant.

Animals↗

Role of prostanoids and lipid peroxides as mediators of the 12-O-tetradecanoylphorbol-13-acetate effect on cell growth.

Confluent cultures of guinea pig smooth muscle cells (SMC) or human fibroblasts (HNF) were treated with 12-tetradecanoylphorbol-13-acetate (TPA). Prostanoid levels were measured by the radioimmunoassay of 6-keto-PGF1 alpha and PGE2, and lipid peroxides were measured by the thiobarbituric acid test for malondialdehyde (MDA). Cells were seeded at low densities, and growth was calculated both from the cell count (Coulter Counter) and the colony number (image analysis). When confluent SMC and HNF were incubated in media alone, 6-keto-PGF1 alpha levels were a function of the TPA concentration, increasing to a maximum at 10(-8) M TPA and then decreasing at higher TPC concentrations. When confluent SMC and HNF were incubated in media containing exogenous arachidonic acid, 6-keto-PGF1 alpha levels again increased to a maximum at 10(-8) M TPA but decreased at higher TPA concentrations only with SMC. The increase in 6-keto-PGF1 alpha levels was much greater in HNF (1310%) than SMC (680%). SMC synthesized similar amounts of 6-keto-PGF1 alpha and PGE2, and the stimulatory effect of TPA was similar with 6-keto-PGF1 alpha and PGE2. Indomethacin (IM) blocked prostanoid synthesis at all TPA concentrations. TPA did not have a significant effect on MDA levels in either cell line. The lipid antioxidants alpha-tocopherol and alpha-tocopherylquinone blocked lipid peroxidation without affecting the stimulation of prostanoid synthesis with TPA. Cell number decreased to a minimum at 10(-8) M TPA in both cell lines. The decrease in cell number was much greater in HNF (72%) than SMC (30%). SMC colony number decreased at 10(-8) TPA and then increased at 10(-6) M TPA. IM did not block the TPA effect on cell number in either cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Metabolism of n-3 polyunsaturated fatty acids and modification of phospholipids in cultured rabbit aortic smooth muscle cells.

The metabolism of the linolenic acid family (n-3) of fatty acids, e.g., linolenic, eicosapentaenoic, and docosahexaenoic acids, in cultured smooth muscle cells from rabbit aorta was compared to the metabolism of linoleic and arachidonic acids. There was a time-dependent uptake of these fatty acids into cells for 16 hr (arachidonic greater than docosahexaenoic, linoleic, eicosapentaenoic greater than linolenic), and the acids were incorporated mainly into phospholipids and triglycerides. Eicosapentaenoic and arachidonic acids were incorporated more into phosphatidylethanolamine and phosphatidylinositol plus phosphatidylserine and less into phosphatidylcholine than linolenic and linoleic acids. Docosahexaenoic acid was incorporated into phosphatidylethanolamine more than linolenic and linoleic acids and into phosphatidylinositol plus phosphatidylserine less than eicosapentaenoic and arachidonic acids. Added linolenic acid accumulated mainly in phosphatidylcholine and did not decrease the arachidonic acid content of any phospholipid subfraction. Elongation-desaturation metabolites of linoleic acid did not accumulate. Cells treated with eicosapentaenoic acid accumulated both eicosapentaenoic and docosapentaenoic acids mainly in phosphatidylethanolamine and the arachidonic acid content was decreased. Added docosahexaenoic acid accumulated mainly in phosphatidylethanolamine and decreased the content of both arachidonic and oleic acids. The following conclusions are drawn from these results. The three n-3 fatty acids are utilized differently in phospholipids. The arachidonic acid content of phospholipids is reduced by eicosapentaenoic and docosahexaenoic acids, but not by linolenic acid. Smooth muscle cells have little or no desaturase activity, but have significant elongation activity for polyunsaturated fatty acids.

Animals↗

[Clinical effect of aztreonam in infections in obstetrics and gynecology].

Aztreonam (SQ 26,776, AZT), a new monobactam antibiotic, was studied in obstetrics and gynecology with the following results. For the study of tissue penetration, 1 g AZT was administered by intravenous drip infusion for 1 hour. The concentration was high in elbow venous blood and uterine arterial blood 60 minutes after the administration. Each uterine tissue concentration other than the endometrium was as high as 26.7-31.7% of the blood level and salpinx and ovary concentration were 25.9% and 5.2%, respectively. Each tissue concentration decreased to less than 0.6 microgram/g in the uterine, the ovary and the salpinx 280 minutes thereafter. In the review of obstetric and gynecologic genital infections, clinical efficacy of AZT was "poor" for 1-endometritis, "poor" for 1-pyometra, "excellent" for 1-puerperal fever, "excellent" (1) and "good" (2) for 3-pelvioperitonitis, "excellent" for 1-parametritis and "good" for 2-infectious lymphocele with overall effective rate of 77.8% (7/9). AZT was microbiologically effective for Gram-negative bacteria, such as E. coli, K. pneumoniae, etc. As for safety, neither side effects nor abnormal laboratory findings in the examination of blood, hepatic function, renal function and urine due to AZT were reported.

Adult↗

[The effect of cefmenoxime in protection against postoperative infection in common gynecological surgery].

Cefmenoxime (CMX) was administered to protect against postoperative infections in 52 cases of cesarean section and 50 cases of total abdominal hysterectomy. These two represent common operations in the gynecological field. Group I was given the agent at a total dose of 14 g (postoperatively 4, 4, 2, 2 and 2 g), group II at a total dose of 10 g (postoperatively 2, 2, 2, 2 and 2 g) and group III at a total dose of 10 g (2 g during operation and postoperatively 2, 2, 2 and 2 g). 1. When comparing the fever index between the groups, group III showed the lowest level regardless of the type of operation. 2. When comparing clinical test values between the groups, low values of white blood cell count (P less than 0.05, P less than 0.01) and erythrocyte sedimentation rate (P less than 0.05) were observed in group III with cesarean section, and significant decreases in white blood cell count (P less than 0.05) and CRP (P less than 0.01, P less than 0.001) were observed in group III with total abdominal hysterectomy. The above results indicate that the administration of CMX during operation was the most effective method of administration for protection against postoperative infections in terms of changes in fever index and clinical test values.

Adult↗