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Biomedical subjects

A C Roy

Publications and source records attributed to A C Roy.

At least 73 records · Page 4Linked to original sources

Plasma levels of 13,14-dihydro-15-keto PGE2 after vaginal application of a new PGE2 film.

To determine the release and absorption profile of prostaglandin E2 from a new vaginal film formulation containing 850 micrograms PGE2, serial plasma levels of 13,14-dihydro-15-keto PGE2 were measured by radioimmunoassay in pregnant women between 16 and 18 weeks gestation. A control group, using placebo vaginal film was included in the study. There was a somewhat uniform increase in the plasma levels of the PGE2 metabolite, reaching peak levels between 4 and 6 hours after application of the film. The findings suggest that this drug formulation could be used clinically when slow constant release of the prostaglandin is required over a period of hours such as in pre-induction cervical ripening of term pregnancy.

Abortion, Induced↗

Multimolecular forms of oxytocinase activity in the human uterus and their inhibition by prostaglandins and cyclic GMP.

Oxytocinase (EC 3.4.11.3) activity was measured in uterine homogenates from pregnant and non-pregnant women using S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN) separately as substrates. There was no significant difference between the specific activity of the enzyme in the pregnant and non-pregnant uterus. The uterine homogenates were also subjected to gel filtration on Ultrogel AcA 22 column and two hydrolyzing activity peaks from the pregnant uterus (PUI, PUII) and three from the non-pregnant uterus (UI, UII, UIII) were obtained. Although the pattern of hydrolysis of the two substrates by the enzyme peaks was similar, the hydrolysis of LN was greater than that of BCN. PUII, UII and UIII showed higher affinity for the substrates than PUI and UI, and the affinity of all isoenzymes was significantly greater for LN than BCN. These uterine oxytocinases appeared to be metallo-aminopeptidases and were potently inhibited by Cu2+, Zn2+ and prostaglandins (PGs). Cyclic GMP (cGMP) and its 8-bromo derivative, however, inhibited only PUI and UI. The divalent cations and PGs were equipotent against the hydrolysis of both substrates, but cGMPs were more effective against BCN hydrolysis. All of these inhibitions depended on the pH of the incubation medium and types of the inhibition by PGs and cGMPs were mixed and uncompetitive respectively. The implications of these findings in relation to human parturition have been discussed.

Aminopeptidases↗

Another look at initiation of human parturition.

Despite our moderate understanding of the physiology of the initiation of labour in various animal species, notably ruminants and rodents, the mechanism in man remains enigmatic. In the initiation process in the human the major role is apparently taken by the placental and fetal membranes, while the fetus may modulate the timing of labour. This review sets out to examine current knowledge of the process of initiating and maintaining parturition in the human.

Adrenal Cortex Hormones↗

Selective inhibition of multimolecular forms of human serum and placental oxytocinase activity by prostaglandins and cyclic GMP.

Ultrogel acrylamide-agarose chromatography was employed for fractionation of oxytocinase isoenzymes from serum of pregnant women and from human placenta. Using S-benzyl-L-cysteine-p-nitroanilide ( BCN ) and L-leucine-p-nitroanilide (LN) as substrates, three activity peaks (PI, PII, PIII) from placenta, and one peak (SI) from serum were identified. SI coincided with PII, and with all isoenzymes the hydrolysis of LN was greater than that of BCN . Prostaglandins E1, E2 and F2 alpha inhibited all oxytocinases , more potently the hydrolysis of LN than BCN and at pH 6.2 than at pH 6.8. Although cyclic GMP and its 8-bromo derivative similarly inhibited these isoenzymes except PIII, they were considerably more effective against the hydrolysis of BCN than LN.

Alprostadil↗

Thromboxane A2 and prostacyclin levels in molar pregnancy.

Plasma levels of thromboxane (TX) A2 and prostacyclin (PGI2), as measured by radioimmunoassay of their respective stable metabolites TXB2 and 6-keto PGF1 alpha, were studied in six molar pregnancies immediately before, immediately following and 24 h after evacuation of the uterus. The mean (SD) levels for TXB2 were 150 (41), 137 (32) and 125 (25) pg/ml respectively, and for 6-keto PGF1 alpha the respective values were 225 (52), 226 (127) and 213 (49) pg/ml. There was no significant difference in the levels of prostanoids between the samples taken at the various time intervals. The concentration of these prostanoids in molar intravesicular fluid was also determined. Their respective mean (SD) pg/ml values were 3682 (760) for TXB2 and 2969 (744) for 6-keto PGF1 alpha. In 15 normal pregnancies of equivalent gestation, the mean amniotic fluid levels of TXB2 and 6-keto PGF1 alpha were 34 (17) and 146 (86) pg/ml respectively. The ability of molar trophoblast to generate the prostanoids from [14C]arachidonic acid in vitro was also demonstrated. Mean (SD) values for TXB2 and 6-keto PGF1 alpha were 12.2 (2.6) and 13.2 (1.8) pg/mg protein/min, respectively. It is likely that the high concentrations of prostanoids in vesicular fluid reflect the synthesizing ability of the villus vesicles. The mole contributes little to the circulatory prostanoids possibly because its villi are deficient in blood circulation.

6-Ketoprostaglandin F1 alpha↗

Intrauterine devices and pelvic inflammatory disease.

There is convincing clinical evidence that PID is more common in IUD users than in users of other contraceptive methods. There appears to be a smaller but significant increase when IUDs are compared with sexually active noncontraceptive users. However, the incidence of PID severe enough to warrant hospitalization is only of the order of 1 to 2 per 1,000 women per year. The question which remains is whether beyond this low figure of moderate and severe disease there is a much higher incidence of subclinical PID which may result in complications for IUD users. Development of a marker such as C-Reactive protein or the split complement component C3d to detect mild PID would prove invaluable in the elucidation of several crucial problems in the clinical management of women using IUDs.

Actinomycosis↗

Cord plasma alpha-fetoprotein values and neonatal jaundice.

Umbilical cord plasma alpha-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean alpha-fetoprotein value of 173 +/- 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 +/- 21.7 mg/L) for the control infants (P less than .001). G-6-PD status and sex did not significantly affect the alpha-fetoprotein values. Using an alpha-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.

China↗

Review: significance of the inhibition by prostaglandins and cyclic GMP of oxytocinase activity in human pregnancy and labour.

The uterotonic action of oxytocin has been known for many decades. This neurohypophysial hormone is thought to play a functional role in human parturition. Since 1968, prostaglandins have also been implicated in parturition. These two groups of uterotonic agents have now a recognized therapeutic role, and are widely used in the induction of labour and in fertility control. However, the mechanism of action and the interrelationship between these endogenous compounds in pregnancy are poorly understood. In this article, the role and interaction of oxytocin, oxytocinase and prostaglandins in human pregnancy and labour have been reviewed. Inhibition of oxytocinase activity by prostaglandins has been suggested as a mechanism in parturition. Possible involvement of cyclic GMP in the initiation of labour has also been discussed.

Aminopeptidases↗

pH dependent inhibition of serum oxytocinase activity by prostaglandins and cyclic GMP.

The effect of pH in the range 6.2 to 7.7 on the inhibition of serum oxytocinase (EC 3.4.11.3) activity by various compounds was studied using S-benzyl-L-cysteine-p-nitroanilide (BCN) as substrate. Prostaglandins E1, E2, F2 alpha, 8-bromo-cGMP, cGMP, indomethacin and polyphloretin phosphate (PPP) produced a dose related pH dependent inhibition of serum oxytocinase. Their effect was maximum at pH 6.2 and minimum at pH 7.7. Hypertonic urea and saline also caused pH dependent inhibition; saline being most active at pH 6.2, and urea at pH 7.7. A similar pH dependent inhibition was found when these compounds were examined for their effect on the hydrolysis of L-leucine-p-nitroanilide (LN) by serum aminopeptidases at pH between 6.2 and 7.7. Although the inhibitors were more effective against the hydrolysis of LN than BCN substrate, cGMP and its 8-bromo derivative were more active against the BCN hydrolysis. cAMP, 8-bromo-cAMP, dibutyryl (db)-cAMP, db-cGMP, AMP, ADP, ATP, GDP, GTP, aspirin, sodium salicylate, paracetamol, theophylline and isobutylmethylxanthine (IBMX) at comparable concentrations and within the same pH range had no effect on the hydrolysis of either substrate. It is concluded that in serum obtained during pregnancy, the hydrolysis of LN may largely be attributed to oxytocinase activity. Thus, inhibition of LN hydrolysis by prostaglandins and other substances may be regarded as inhibition of oxytocinase activity.

Aminopeptidases↗

Inhibition of serum oxytocinase activity by prostaglandins.

The effect of prostaglandins (PGs) and other compounds on human serum oxytocinase (EC 3.4.11.3) activity in vitro was studied by a sensitive assay using S-benzyl-L-cysteine-p-nitroanilide as substrate. PGE1, PGE2 and PGF2 alpha significantly inhibited serum oxytocinase activity in a dose-related manner and in decreasing order of potency. cGMP, 8-bromo-cGMP, indomethacin, polyphloretin phosphate, hypertonic saline and urea were also active. cAMP, db-cAMP, 8-bromo-cAMP, db-cGMP, 5'-AMP, 5'-ADP, 5'-ATP, 5'-GDP, 5'-GTP, aspirin, sodium salicylate, paracetamol, theophylline and IBMX did not inhibit the enzyme activity. The results suggest that the oxytocic action of prostaglandins may be due, at least in part, to an inhibition of oxytocinase activity.

Aminopeptidases↗

Management of disrupted sternotomy.

Seventeen out of 929 consecutive patients (1.8%) who underwent open-heart surgery during the last three years developed dehiscence of the sternotomy. Infection was the most common cause of dehiscence and occurred more often after reopening of the incision to control bleeding or relieve tamponade. We describe a one stage closure which was used in all 17 cases. A successful result was obtained in 16 cases, discharge from hospital occurring between 21 and 51 days after closure.

Humans↗

Opiates, cyclic nucleotides, and xanthines.

In rat brain homogenate, opiates exert a dose-related inhibition of PGE-stimulated cyclic (AMP) formation. This effect is stereospecific and is correlated with agonist potency. Naloxone antagonizes heroid in a dose-related way, without, at effective concentrations, itself inhibiting PGE-stimulated cyclic AMP formation. In morphine-dependent rats, intracerebroventricular injection of cyclic AMP intensifies and of dibutyryl cyclic GMP diminishes precipitated abstinence effects. In naive rats, the xanthines, theophylline and 3-isobutyl-1-methylxanthine, produce a quasimorphine-abstinence syndrome that is readily suppressed by heroin and intensified by nalosone. In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase. These findings are concistent with these views: (a) The opiates specifically inhibit an adenylate cyclase of morphine-sensitive neurons that is sensitive to stimulation by PGEs. (b) Opiate agonist action is associated with the lowering of a neuronal cyclic AMP. (c) Both the morphine-abstinence syndrome in dependent rats and the quasi-abstinence syndrome in naive rats are associated with a rise in this neuronal cyclic AMP. (d) There are two types of endogenous humoral mediator acting on morphine-sensitive neurons, one of which is morphine-like and the other antimorphine-like in action.

3',5'-Cyclic-AMP Phosphodiesterases↗