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Biomedical subjects

N Sagawa

Publications and source records attributed to N Sagawa.

At least 91 records · Page 5Linked to original sources
PubMed1985

[Correlation between the inhibition of renin-angiotensin system and antihypertensive effect of MK-421 and captopril in 2-kidney, 1-clip renal hypertensive rats after single and repeated oral administration of MK-421 or captopril].

The angiotensin converting enzyme (ACE) activity in tissues and plasma renin activity (PRA) were measured in 2-kidney, 1-clip renal hypertensive rats (2K-RHR) and normotensive rats after a single and 3-weeks oral administrations of ACE inhibitors such as MK-421 and captopril. In the single dose study, MK-421 (1 and 3 mg/kg) and captopril (3 and 10 mg/kg) inhibited the ACE activities in kidney, aorta and plasma in a dose-dependent fashion. The inhibition of ACE activity in kidney or aorta was observed for a longer time than that in plasma. PRA took a time course reversal to that of plasma ACE activity. In the 3-weeks repeated dose study, the ACE activity in kidney and aorta was strongly inhibited after the administration of each ACE inhibitor, while there was no significant change in lung ACE activity at any time point examined. The plasma ACE activity markedly elevated after the administration of each agent. PRA significantly increased after the administration of either agent, while the plasma angiotensin II level was significantly inhibited. These results indicate that the inhibition of the ACE activity in blood vessel or kidney correlate well with the antihypertensive activity in 2K-RHR after a single and repeated administration of both ACE inhibitors, but not well with the inhibition of plasma ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

A case of postpartum hemolytic uremic syndrome with severe elevations of liver enzymes.

An unusual case of multifocused postpartum thrombotic microangiopathy was encountered in a woman with pregnancy-induced hypertension, which presented clinical features different from those generally seen in postpartum hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. These changes included acute disseminated intravascular coagulation, severe elevations of liver enzymes, severe renal dysfunction, and hemolytic anemia. The patient was treated successfully with heparin, gabexate mesilate, furosemide, fresh whole blood, and large doses of corticosteroid with antibiotics, and she recovered completely without sequelae. The hypothetical pathogenesis of the complex symptoms of this catastrophic clinical condition is proposed.

Adult↗
PubMed1985

[The responses of isolated uterine arteries from pregnant sows to vasoconstrictive agents].

Isometric contractions of isolated uterine arteries, mesenteric arteries and the thoracic aortae of nonpregnant and pregnant sows were measured in a modified Krebs-Henseleit solution in order to investigate the characteristics of the uterine artery responsiveness to vasopressor substances during pregnancy. Contractile response (delta T) of the uterine artery from pregnant sow to angiotensin II(A II) was significantly smaller than that from nonpregnant animal. On the other hand, delta T of uterine artery from pregnant sow to norepinephrine (NE) was greater than that from nonpregnant animal. NE-induced delta T of preparations from both pregnant and nonpregnant sow were suppressed nearly to the same level following the treatment of phentolamine, or verapamil in the incubation medium of 2.5mM Ca2+. In the Ca2+-free (EDTA 1mM) incubation medium, the responses decreased to the minimum degree. These results imply that conspicuous refractoriness of the uterine artery to A II during pregnancy is due to the changes in the characteristics of the uterine vascular wall, and the enhanced responsiveness to NE of the uterine artery may be due to the increased sensitivity in alpha-adrenergic receptor on the vasculature with the increase in Ca ion influx.

Angiotensin II↗
PubMed1985

[Assessment of fetal lung maturity by determination of phosphatidylglycerol in human amniotic fluid].

The enzymatic method for the specific quantification of phosphatidylglycerol (PG) and phosphatidylcholine (PC) was described in detail in this paper. Under the present assay conditions, as little as 2 nmoles of PG or PC was accurately measured. The possibility of contamination of cardiolipin and bilirubin in amniotic fluid was eliminated by chromatography on a silicic acid column. Using 275 amniotic fluid samples from uneventful pregnancies, fetal lung maturity was assessed by using a variety of parameters including PG and PC determination. Based on the results of the present investigation, critical concentrations of PG and PC were determined to be 0.36 and 3.0 mumoles/dl, respectively. 239 infants who had more than the critical PG concentration were all associated with normal respiratory function except 3 cases (false-positive rate, 1.3%). 30 out of 36 infants with a PG value lower than this level developed respiratory distress syndrome after birth (false-negative rate, 16.7%). These results indicated that the PG determination was the most accurate predictor of fetal lung well-being prior to birth among the clinical tests so far reported.

Amniotic Fluid↗
PubMed1985

[Fetal maturation and amniotic fluid levels of catecholamines and their metabolites].

Phosphatidylglycerol (PG), a phospholipid closely associated with fetal lung maturity, appears in the amniotic fluid (AF) of complicated pregnant women much earlier than it usually increases during uneventful pregnancy. In this study, AF PG levels, measured by an enzymatic method, were correlated with AF concentrations of catecholamines (CAT) and the deaminated metabolites of dopamine (3,4-dihydroxyphenylacetic acid; DOPAC) and norepinephrine (3,4-dihydroxyphenylglycol; DOPEG), all of which were determined by radioenzymatic assay. AF concentrations of CAT increased with the advance of gestation especially after 36 weeks of gestation, when clinically apparent fetal distress was not present. Three to four fold higher levels of DOPAC and DOPEG over their parent CAT were found in AF. Even prior to 37 weeks of gestation, high concentrations of CAT were found in the pregnancies complicated with fetal distress, and significant correlation was noted for PG versus dopamine (p less than 0.005), norepinephrine (p less than 0.05) epinephrine (p less than 0.02) and DOPEG (p less than 0.05), but not DOPAC. Such a correlation was not observed after 37 weeks of gestation. These findings suggest that fetal CAT plays a primary role in developing fetal lung maturation and that AF PG and CAT increase as a response to chronic distress, only before 37 weeks of gestation.

Adrenal Glands↗
PubMed1984

Role of sex steroid hormones in relative refractoriness to angiotensin II during pregnancy.

Normal human pregnancy is associated with significant vascular refractoriness to the pressor effects of infused angiotensin II, and in women destined to develop pregnancy-induced hypertension, this refractoriness is lost several weeks before the onset of hypertension. The plasma concentrations of sex steroid hormones gradually increase throughout pregnancy. In the present study, the effect of infusion of 17 beta-estradiol (E2), progesterone, or 5 alpha-dihydroprogesterone on the pressor response to infused angiotensin II (0.002 to 0.1 micrograms X min-1 X kg-1) was evaluated in eight unanesthetized and chronically instrumented nonpregnant ewes. Pressor response to infused angiotensin II (0.02 to 0.1 micrograms X min-1 X kg-1) was significantly suppressed by a 60-minute infusion of E2 (0.8 micrograms X kg-1), whereas infusion of progesterone (4 micrograms X min-1 X kg-1) or 5 alpha-dihydroprogesterone (0.8 micrograms X min-1 X kg-1) did not affect the pressor response. Neither the acid-base status, plasma renin activity, nor serum electrolytes were altered by the administration of E2 or progesterone. These results indicate that E2 may play an important role in the refractoriness to infused angiotensin II during pregnancy, and that this refractoriness by E2 is not mediated by changes in chemoreceptor reflex, renin-angiotensin system, or serum electrolytes, but more likely by the changes in the characteristics of the vascular wall.

5-alpha-Dihydroprogesterone↗
PubMed1984

[Effect of nicotine on uterine blood flow and antagonistic effect of prostaglandin I2 derivative (OP-41483) in pregnant ewes].

In order to elucidate the mechanism of the detrimental effect of smoking on uteroplacental circulation in pregnant women, and to confirm the protective effect of PGI2 derivative (OP-41483) against the effect, hemodynamic responses to various doses of nicotine infusion (0.25-1.0 mg/min) were measured before and during the OP-41483 infusion in chronically instrumented pregnant ewes. Moreover, the isometric tension responses of spiral strips of sow uterine arteries to the nicotine and norepinephrine perfusion were also measured using an in vitro technique. The results were as follows: Maternal mean arterial blood pressure (MAP) and the cardiac output were increased by the intravenous infusion of various doses of nicotine; however the uterine blood flow (UBF) decreased consistently in a dose-dependent fashion, and it decreased 20.4% from the control level following the infusion of 1.0 mg/min nicotine, suggesting a detrimental effect on the fetus. During the infusion of OP-41483 (25 micrograms/min), nicotine induced MAP increases were suppressed at all test doses and the decrease in UBF was lessened by 22% of control delta UBF on doses of 1.0 mg/min nicotine. In the muscle chamber, the tension increase in uterine artery strips of nonpregnant sows to various nicotine concentrations (10(-7)-10(-4) M) were suppressed by the preliminary treatment with phentolamine (0.1 mg/min), and the responses to norepinephrine were also suppressed by the preliminary treatment with a low concentration of nicotine (10(-6) M) in the buffer bath.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Changes in the mechanical forces of cervical distention before and after rupture of the membranes.

Rupture of the membranes at term, when performed at an appropriate time, is clinically known to induce or accelerate labor. In the present study, the mechanisms of cervical softening and onset and/or enhancement of labor after spontaneous or artificial rupture of the membranes were investigated. The mechanical forces involved in cervical distention at the area where the fetal head is in contact with the cervix were mathematically estimated before and after rupture of the membranes, and the difference between forces under both conditions was calculated. Rupture of the membranes, when occurring either spontaneously or artificially at an appropriate time, has been found to result in an increase of the force of distention in the cervix where it comes into contact with the head. Thus, the increased force against the cervix, as seen by stretching, through the possible increased release of prostaglandins, results in cervical softening and initiation and/or enhancement of labor.

Cervix Uteri↗
PubMed1983

The effects of polyamines and aminoglycosides on phosphatidylinositol-specific phospholipase C from human amnion.

The effects of polyvalent cations (polyamines and aminoglycoside antibiotics) on Ca2+-dependent phosphatidylinositol-specific phospholipase C activity of human amnion tissue were examined. In the presence of 1 mM Ca2+, the hydrolysis of phosphatidylinositol (2 mM) by phospholipase C was increased greatly (240-560% of control) by spermine (0.4 mM), spermidine (1 mM), neomycin (0.1 mM), gentamicin (0.2 mM), kanamycin (0.4 mM) and streptomycin (0.8 mM). Putrescine and cadaverine (0.1-2.0 mM), however, stimulated phospholipase C activity only slightly. The effects of spermidine, spermine and gentamicin on phospholipase C activity were characterized and found to be dependent upon the concentrations of phosphatidylinositol, Ca2+ and the particular polyvalent cation. At low concentrations of phosphatidylinositol and Ca2+ the predominant effect of polyamines and aminoglycosides was to inhibit phospholipase C activity. When the concentrations of phosphatidylinositol and Ca2+ were increased, spermidine, spermine and gentamicin stimulated phospholipase C activity. In the presence of 16 mM Ca2+, however, phospholipase C activity was maximal and was unaffected by either polyamines or aminoglycosides. At all concentrations of Ca2+ examined, the maximal stimulation of phospholipase C activity by a given polyvalent cation occurred at a fixed molar ratio of the particular polyvalent cation to phosphatidylinositol. Polyamines and aminoglycosides appeared to modulate the Ca2+ requirement for phospholipase C activity, but could not substitute completely for Ca2+. The activities of phospholipase A2, diacylglycerol lipase, monoacylglycerol lipase and diacylglycerol kinase in amnion tissue were unaffected by any of the polyvalent cations examined. It is proposed that any in vivo influences (stimulatory or inhibitory) of polyamines and aminoglycosides on amnion phospholipase C activity would depend upon the effective concentrations of Ca2+ and phosphatidylinositol.

Aminoglycosides↗
PubMed1983

[Effects of indomethacin on renal and uterine blood flow and pressor responsiveness to angiotensin II or norepinephrine in pregnant dogs].

Pressor responsiveness to angiotensin II (A II) or norepinephrine (NE) in anesthetized nonpregnant and pregnant dogs, and the changes in renal blood flow (RBF) and uterine blood flow (UBF) elicited by the pressure rise in pregnant dogs were studied. Intervention of prostaglandins (PGs) in these hemodynamic responses was also examined, comparing the responses before and after the administration of indomethacin (IDM). The pressor responsiveness to the pressor substances was diminished in near term pregnant dogs in common with normal human pregnancy, and the refractoriness disappeared after the administration of IDM. RBF decreased following the infusion of A II or NE, and IDM enhanced the responses. A characteristic increase in UBF was observed following the infusion of A II exhibiting the maximum response at a dose of 0.05 microgram/kg, while it decreased following the infusion of NE, and these responses remained almost unchanged after IDM administration, although there was a 24.2% decrease in the base line value of UBF. It seems appropriate to conclude that PGs play a pivotal role in the development of the relative vascular refractoriness to infused pressor substances characterizing normal pregnancy, and also in preservation of RBF and UBF during pregnancy. Moreover, PGs attenuate the response of the renal vascular bed as well as systemic vascular bed to the pressor substances. However, the refractoriness of uterine vascular bed to A II remained almost unchanged regardless of PGs synthesis, suggesting the existence of another competitive factor involved in the effect of A II.

Angiotensin II↗
PubMed1981

Diacylglycerol metabolism and arachidonic acid release in human fetal membranes and decidua vera.

Diacylglycerol lipase activity has been demonstrated in human fetal membranes and decidua vera tissues. The specific activity of the enzyme is highest in the microsomal fraction of decidua vera tissue. The acylester bond at the sn-1 position of 1,2-diacyl-sn-glycerol is hydrolyzed followed by release of the fatty acid at the sn-2 position. The diacylglycerol lipase activity present in the microsomal fraction of decidua vera tissue hydrolyzes preferentially a diacylglycerol containing an arachidonoyl group in the sn-2 position. Monoacylglycerol lipase activity was also demonstrated in these tissues. The specific activity of monoacylglycerol lipase was significantly greater than that of diacylglycerol lipase and catalyzed preferentially the hydrolysis of monoacylglycerols containing an arachidonyl group in the sn-2 position. Based on the subcellular distribution and the differential effects of various inhibitors, we suggest that the monoacylglycerol lipase and diacylglycerol lipase in decidua vera tissue are 2 distinct enzymes. Diacylglycerol kinase specific activity was examined also and was found to be 4-5 times greater in amnion than in either chorion laeve or decidua vera. The importance of diacylglycerol metabolism in the mechanism of arachidonic acid release and prostaglandin biosynthesis is discussed.

Arachidonic Acid↗
PubMed1980

Application of cephalosporins to obstetrics and gynecology: transfer of cefazolin and cephalothin to uterine tissue.

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In tthe perimetrium, levels were 154 microgram/gm for cefazolin and 24.1 microgram/gm for cephalothin; in the myometrium, 109.5 microgram/gm for cefazolin, and 15.5 microgram/gm for cephalothin; and in the endometrium, 98.9 microgram/gm for cefazolin and 10.4 microgram/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 microgram/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40-70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.

Adult↗