Plasma prostaglandin F 2-alpha levels in dysmenorrehic women

The conversion of dihydrothebainone to codeine or thebaine has been achieved in high yield. Bromination and dehydrobromination constructs the 4,5-oxide bridge to give 1-bromo- and 1,7-dibromodihydrocodeinone which yield dihydrocodeinone practically quantitatively after catalytic debromination. Ketalization and acid-catalyzed elimination of methanol give excellent yields of delta6-dihydrothebaine to which is added methyl hypobromite using N-bromoacetamide in methanol. The action of potassium tert-butoxide in Me2SO on the resulting 7-bromodihydrocodeinone dimethyl ketal gives codeinone dimethyl ketal selectivity at 60 degrees while at 120 degrees thebaine is the exclusive product. Hydrolysis to codeinone and borohydride reduction give codeine in 70% overall yield. The bromo intermediates in the formation of the 4,5-oxide bridge have been examined. 1,5beta, 7alpha-Tribromodihydrothebainone has been identified as the main product in the tribromination of dihydrothebainone.     

Radioimmunoassay for urinary metabolites of prostaglandin F2alpha

Antibodies against the main urinary metabolite of PGF2alpha in the human, 5alpha, 7alpha-dihydroxy-11-ketotetranorprosta-1,16-dioic acid, were raised in rabbits. The compound was coupled selectively in the omega position to bovine serum albumin prior to injection. The resuling antibodies did not distinguish between tetranor compounds varying only in structure at the omega carbon, and thus the assay could be used also for other metabolites of PGF2alpha, e.g. the main urinary metabolite in the guinea pig, 5alpha,7alpha-dihydroxy-11-ketotretranorporstanoic acid. Labeled ligands for the assays were prepared either in vivo by injection of [17, 18-3H]-PGF2alpha into humans after several days treatment with indomethacin, or in vitro by incubation of [17, 18-3H]-15-keto-13, 14-dihydro-PGF2alpha with mitochondria from rat liver. The sensitivity of the assay was 10 pg or 4 pg with these two preparations, respectively. The assay was employed for a number of measurements: normal daily excretion in a number of humans; excretion of urinary metabolites during treatment with prostaglandin synthetase inhibitors in human subjects, or after intravenous injection of PGF2alpha; excretion during human pregnancy; and prostaglandin production in the guinea pig during normal estrous cycles and pregnancies and after estrogen treatment. The results of these studies were in several cases compared to similar measurements earlier performed using mass spectrometric methods, and were found to agree well. Thus, this radioimmunoassay provides a simple and accurate method for estimating prostaglandin production, particularly suitable for long-term studies and for cases where repeated blood sampling must be avoided.     

Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management

BACKGROUND: Postpartum cerebral angiopathy as a cause of hemorrhagic stroke in young women is not well recognized. It is unknown whether this disorder represents a true inflammatory vasculitis or transient vasoconstriction related to the hormonal events of pregnancy and the postpartum period. CASE DESCRIPTION: A 39-year-old woman presented with postpartum intracranial hemorrhage and, 32 months later, with subarachnoid hemorrhage, following normal pregnancies. Cerebral angiography obtained after each stroke demonstrated diffuse irregularity of branches of the middle cerebral arteries consistent with a diffuse vasospastic process or classic vasculitis. Neurological deficits resolved and results of a transcranial Doppler study normalized after a short course of high-dose corticosteroids following the second stroke. CONCLUSIONS: Postpartum cerebral angiopathy should be considered in the differential diagnosis of recurrent intracranial hemorrhagic stroke in young women. Recognition of this condition may preclude treatment with potentially toxic therapies for vasculitis and will have important implications for counseling women on subsequent pregnancies.     

Management of postpartum hemorrhage

Postpartum hemorrhage remains a source of maternal morbidity and mortality in modern obstetric medicine. While the risk factors for postpartum hemorrhage are well described, many patients who develop this complication have no known antenatal risk factors. Therefore, in every delivery the attending physician must be vigilant for signs of hemorrhage. Paramount to a successful outcome is the efficient enactment of a logical plan. Uterine atony causes more than 90 percent of cases of postpartum hemorrhage. Lower genital tract lacerations and retained placental products are the most common causes of hemorrhage when the uterus is firm. Successful treatment of postpartum hemorrhage requires the prompt recognition of ongoing bleeding, followed by uterine massage and oxytocin administration. The intramuscular administration of ergot or prostaglandin preparations can help with refractory bleeding. Most deaths from postpartum hemorrhage occur not because of brisk blood loss, but because of the ineffective management of continuous low-level bleeding.     

Dexamethasone inhibits the pyrogenic activity of prostaglandin F2 alpha, but not prostaglandin E2

The effect of dexamethasone on prostaglandin (PG) E2- and PGF2 alpha-induced fever was studied in rats. Intracerebroventricular injection of PGE2 and PGF2 alpha (500 ng) induced increases in body temperature (maximal temperature rises of 0.97 +/- 0.13 degrees C and 0.78 +/- 0.18 degrees C, respectively, vs. vehicle 0.12 +/- 0.09 degrees C) of unrestrained rats maintained within the thermoneutral zone. PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2 alpha. Subcutaneous pre-administration of dexamethasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal temperature rise of 1.00 +/- 0.08 degrees C), but completely prevented the pyrogenic activity of PGF2 alpha (maximal temperature rise of 0.16 +/- 0.16 degrees C). Neither PGE2- nor PGF2 alpha-induced fever was significantly altered (maximal temperature rises of 0.90 +/- 0.11 degrees C and 0.64 +/- 0.14 degrees C, respectively) by intraperitoneal administration of indomethacin (2 mg/kg). These results demonstrate for the first time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of some prostaglandins, possibly via suppression of the synthesis of corticotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.     

Radioimmunoassay of main urinary metabolite of prostaglandin F2alpha

Radioimmunoassay of 5alpha, 7alpha-dihydroxy-11-keto-tetranorprosta-1,16-dioic acid, main urinary metabolite of prostaglandin F2alpha (PGF2alpha), was performed using an antiserum produced in the rabbit. The antibody in 100 mu1 of 1,600-fold diluted antiserum binds with 60 picograms of metabolite. The main urinary metabolite level fell when flufenamic acid, a prostaglandin synthetase inhibitor, was given to rats. In contrast, it was significantly elevated when PGF2alpha was administered.     

Use of combination prostaglandin F2alpha and hypertonic saline for midtrimester abortion

Midtrimester abortion was induced by intramniotic prostaglandin F2alpha in combination with hypertonic saline alone in 102 others. Abortion time and duration of hosptial stay were shorter with the prostaglandin-saline combination.     

Biosynthesis of prostaglandin F2alpha from arachidonic acid and prostaglandin endoperoxides in the uterus

Formation of prostaglandin F2Alpha in the cow and guinea pig uterus microsomes was studied using 14C-labeled arachidonic acid and prostaglandin H2. The total conversion of arachidonic acid was of a low order and underwent fluctuations during the estrous cycle of the guinea pig, being highest towards the end of the cycle. Injections of beta-estradiol-3-benzoate also resulted in higher activity of the uterine prostaglandin synthetase. The uterine prostaglandin synthesizing system appeared to differ in several respects from that present in seminal vesicles, with regard to the proportions of the products formed and the effects of various agents, e.g. reduced glutathione. An inhibiting factor which supressed the fatty acid cyclo-oxygenase was found to be present in uterine preparations. Prostaglandin endoperoxide (prostaglandin H2) was very efficiently reduced to prostaglandin F2alpha by cow and guinea-pig uterus microsomes. Prostaglandin G2 also gave rise to prostaglandin F2alpha. Prostaglandin E2, on the other hand, was not reduced. Both the inhibiting factor and the endoperoxide reducing activity are likely to be parts of a highly specialized mechanism that modulates prostaglandin F2alpha formation in the uterus.     

Anuria following silver nitrate irrigation for intractable bladder hemorrhage

Intravesical silver nitrate has been used for intractable bladder hemorrhage. A case of anuria resulting from this technique is reported. The etiology of anuria in this patient was probably owing to obstruction from deposition of silver salts. The level of obstruction was the ureterovesical junction on 1 side and the collecting ducts at the renal papillae on the other side. Therapy consisted of vigorous endoscopic evacuation of deposited silver salts from the bladder and hemodialysis with good results.     

Preoperative cervical dilatation by small doses of prostaglandin F 2 alpha

To clarify the role of Ca ion in the rising phase of the sinoatrial (S-A) node action potential, the sigmoidal relationship between the maximum rate of rise of the action potential and the maximum diastolic potential was examined at various concentrations of Ca. The membrane potential was changed by applying a current across a single sucrose gap. The sigmoidal curve shifted toward the positive potential without a change in maximum value when the Ca concentration was increased from nominal "zero" to 10 mM. Therefore, it is concluded that Ca ion modifies the inactivation process of Na current which is responsible for the rapid rising phase of the S-A node action potential. The duration of the action potential and the maximum diastolic potential were decreased with an increase in Ca concentration. The observation that the overshoot of the action potential increased by 12 mV for a tenfold increase in concentration of Ca (within the range of 0.1-5.0 mM) suggests that the inward current of Ca ion may be responsible for the overshoot of the S-A node action potential.     

Human intestinal epithelial cells respond to Cryptosporidium parvum infection with increased prostaglandin H synthase 2 expression and prostaglandin E2 and F2alpha production

Cryptosporidium parvum is an important cause of diarrhea in humans and several animal species. Prostaglandins play a central role in regulating intestinal fluid secretion in animal models of cryptosporidiosis, but their cellular sources and mechanisms of induction are unclear. Here, we show that C. parvum infection directly activates prostaglandin H synthase 2 expression and prostaglandin E2 and F2alpha production in human intestinal epithelial cells.     

Termination of abnormal intrauterine pregnancies with intramuscular administration of dihomo 15 methyl prostaglandin F 2alpha

A synthetic compound, 2a, 2b dihomo 15 (S) 15 methyl prostaglandin F 2 alpha methyl ester given 8-hourly by intramuscular injection was used to terminate pregnancies in 72 patients with a missed abortion, intrauterine fetal death, molar or anencephalic pregnancies. Treatment was successful in all cases. A 4 mg dose of loperamide given orally at 15 to 30 minutes before the injection of prostaglandin analogue prevented diarrhoea as a side effect.     

Suppression of evoked IPSPs by arachidonic acid and prostaglandin F2 alpha

Arachidonic acid (AA) and certain prostaglandins appear to antagonize GABAA receptors in synaptoneurosomes [18]. We report here that perfusing hippocampal slices with AA or prostaglandin F2 alpha diminishes evoked IPSP conductance and increases CA1 pyramidal cell input resistance. The effects of the two compounds were similar, though not identical, in time course, magnitude, and response to washout. These findings suggest that high levels of AA and its metabolites may bias neurons towards excitation.