Cytoprotective and antisecretory properties of a non-diarrheogenic and non-uterotonic prostacyclin analog: U-68, 215

U-68,215 [15-Cyclohexyl-9-deoxo-13, 14-dihydro-2′, 9a-methano-4,5,6,16,17,18,19,20-octanor-3-oxa-3,7-(′1,′3-interphenylene)-PGE₁] is a stable prostacyclin analog. When given orally to rats, it is cytoprotective for the stomach (ED₅₀: 0.8 μg/kg) and the intestine (ED₅₀: 22 μg/kg), is gastric antisecretory (ED₅₀: 35 μg/kg) and antiulcer (aspirin) (ED_{50: 5 μg/kg}). The oral antisecretory ED₅₀ in dogs in 50 μg/kg. It has a long duration of gastric cytoprotection: 8–10 hours compared to 3 hours for 16, 16-dimethyl PGE₂ Unlike most prostaglandins of the E type, it is not diarrheogenic (not enteropooling), it does not induced cellular proliferation of the gastroeintestinal mucosa, when given twice a day for eight days, it is not uterotonic (in monkeys), and it does not prevent embryo implantation in hamsters. It ihibits platelet aggregation (ED₅₀: 300 μg/kg), but does not promote bleeding from cut vessels nor from gastric ulcers. U-68,215 lowers blood pressure at a n oral dose correponding to 1–5 time the antisecretory ED₅₀ in rats and dogs, and to 150 times the cytoprotective ED₅₀ in rats. It may be of therapeutic value in the treatment of conditions where inhibition of gastric acid secretion is desirable, e.g., gastric and duodenal ulcer, and in conditions responding to cytoprotection, e.g., stress ulcers, hemorrhagic gastritis and gastric erosions associated with nonsteroidal antiinflammatory drugs.     

Synthesis and biological evaluation of 1-(benzenesulfonamido)-2-[5-(N-hydroxypyridin-2(1H)-one)]acetylene regioisomers: a novel class of 5-lipoxygenase inhibitors

A hitherto unknown class of linear acetylene regioisomers were designed such that a SO₂NH₂ group was located at the ortho-, meta-, or para-position of the acetylene C-1 phenyl ring, and a N-hydroxypyridin-2(1H)-one moiety was attached via its C-5 position to the C-2 position on an acetylene template (scaffold). All three regioisomers inhibited 5-lipoxygenase (5-LOX), where the relative potency order was 2-SO₂NH₂ (IC₅₀ = 10 μM) >3-SO₂NH₂ (IC₅₀ = 15 μM) >4-SO₂NH₂ (IC₅₀ = 68 μM) relative to the reference drug nordihydroguaiaretic acid (NDGA; IC₅₀ = 35 μM). The 2-SO₂NH₂ regioisomer (ED₅₀ = 86.0 mg/kg po) exhibited excellent oral anti-inflammatory (AI) activity that was more potent than aspirin (ED₅₀ = 128.9 mg/kg) and marginally less potent than ibuprofen (ED₅₀ = 67.4 mg/kg). The N-hydroxypyridin-2(1H)one moiety provides a novel pharmacophore for the design of cyclic hydroxamic mimetics capable of chelating 5-LOX iron for exploitation in the design of 5-LOX inhibitory AI drugs.     

Comparison of three subcutaneous modes of prostaglandin F2α administration for pregnancy termination in the hamster

Dose response relationships for pregnancy termination in hamsters following administration of prostaglandin F_2α (PGF_2α by three subcutaneous methods were determined in 526 hamsters. The median effective dose (ED₅₀) for PGF_2α given as a single subcutaneous injection in 500 μl of saline was 22.2 μg. Administration of the prostaglandin with an Alzet® osmotic minipump (subcutaneous insertion for 24 hours) required 1.35 times more PGF_2α (ED₅₀ = 30.0 μg). The least effective method of prenancy termination in the hamster involved administration of PGF_2α by a single subcutaneous injection in 20.4 μl of saline (the same volume delivered by the minipump in 24 hours); the ED₅₀ for this method of administration was 41.3 μg of PGF_2α.     

The optimum sevoflurane concentration for supraglottic airway device Blockbuster™ insertion with spontaneous breathing in obese patients: a prospective observational study

Background

Airway management of the obese patient presenting for surgery is more likely to be a challenging problem. Supraglottic airway device has been adopted as a bridge to connect ventilation and tracheal intubation in obese patients who would be suffered with difficult intubation. The optimum sevoflurane concentration for supraglottic airway device insertion allowing spontaneous breathing in 50% of obese patients (ED₅₀) is not known. The purpose of this study was to determine the ED₅₀ of sevoflurane for supraglottic airway device Blockbuster? insertion with spontaneous breathing in obese patients requiring general anesthesia.

Methods

Thirty elective obese patients (body mass index 30-50 kg/m²) undergoing bariatric surgery were recruited in this study. The predetermined target sevoflurane concentration (initiating at 2.5% with 0.5% as a step size) was sustained for >5 min using a modified Dixon’s up-and-down method, and then the supraglottic airway device Blockbuster? was inserted. The patient’s response to supraglottic airway device insertion was classified as either ‘movement’ or ‘no-movement’. The ED₅₀ of sevoflurane were determined by calculating the midpoint concentration of crossover point from ‘movement’ or ‘no-movement’ response.

Results

The ED₅₀ of sevoflurane for supraglottic airway device Blockbuster? insertion in obese patients calculated using up-and-down method were 2.50?±?0.60%. The ED₅₀ and ED₉₅ (95% confidence interval) obtained by probit regression analysis were 2.35 (1.28–3.42) % and 4.03 (3.16–17.83) % for supraglottic airway device Blockbuster? insertion, respectively.

Conclusion

We conclude that the optimum end-tidal sevoflurane concentration required for the supraglottic airway device Blockbuster? insertion allowing spontaneous breathing in 50% of obese patients (ED₅₀) is 2.5?±?0.6%.

Trial registration

Chinese Clinical Trial Registry, ChiCTR-IPR-16009071, Registered on 24 August 2016.

     

Mechanism of action of suprofen, a new peripheral analgesic, as demonstrated by its effects on several nociceptive mediators

Suprofen is a new potent, orally effective non-narcotic analgesic agent having a potent inhibitory action on prostaglandin (PG) biosynthesis. Recent experiments have shown that suprofen inhibits uterine hyperactivity induced by the physiological substances, arachidonic acid, bradykinin (BK) and PGF_2α. The present study explores the possibility that the analgesic activity of suprofen may involve multiple mechanisms of interaction with PGs, inhibiting synthesis at low doses and with higher doses possibly directly interacting with PGs and other physiological mediators of nociception at a common site. Experiments in mice have shown that suprofen antagonizes abdominal stretching induced by the physiological precursor of PG release, arachidonic acid (ED₅₀ = 0.07 mg/kg, p.p.), and by the nociceptive agents acetylcholine (ACh) (ED₅₀ = 1.7 mg/kg, p.o), BK (ED₅₀ = 65 mg/kg, p.o.) acetic acid (HAC) (H⁺ ion; ED₅₀ = mg/kg, p.o), and PGE₂, itself (ED₅₀ = 20.2 mg/kg, i.p.). In rabbits, i.a. administered suprofen (ED₅₀ = 0.98 mg/kg) blocked the reflex discharge of spinal sensory neurons evoked by BK (2 to 8 μg, i.a). The analgesic activity of suprofen may involve multiple mechanism of interaction with PGs and other mediators, including BK; suprofen blocks the nociceptive actions of PGs by inhibiting their formation, via the cyclooxygenase pathway, and possibly at PG sites of action, probably at peripheral nerve endings.     

Enzyme-Linked Immunosorbent Assays for Detection of Xylem-Limited Bacteria: Use of Trinder Reagent

Quantitation and detection of xylem-limited bacteria with an enzyme-linked immunosorbent assay with a peroxidase conjugate is described. The use of the Trinder reagent (4-aminoantipyrine) allows the determination of extremely small quantities of peroxidase with no precipitate formation or inactivation of the enzyme by H₂O₂. Comparison of the enzyme-linked immunosorbent assay method with microscopic and histochemical tests for the presence of the phony peach disease bacterium in 9-year-old “June Gold” peach trees gave comparable results. The peroxidase conjugate with the Trinder reagent is more sensitive than the alkaline phosphatase conjugate typically used for enzyme-linked immunosorbent assay quantitation.     

An inhibitor of arachidonic acid metabolism stimulates luteinizing hormone (LH) release from cultured pituitary cells

5, 8, 11, 14 eicosatetraynoic acid (“ETYA”, Roche 3-1428) is a competitive inhibitor of arachidonic acid metabolism. It effectively inhibits the action of both the lipoxygenases and the fatty acid cyclooxygenases both of which utilize arachidonic acid as a substrate. In the present work, we have shown that ETYA stimulates luteinizing hormone (LH) release from cultured pituitary cells (ED₅₀ = 10 μg/ml). Stimulation is not due to contaminants present in the preparation, since highly purified ETYA (characterized by GC-MS) stimulates release, while contaminants removed by silicic acid chromatography do not. In addition, neither oxidized solutions of ETYA nor arachidonic acid itself stimulate LH release. ETYA stimulated release is dose dependent and is inhibited by ions which antagonize Ca²⁺ action. The observation that neither indomethecin (10, 100 μg/ml) nor meclofenamate (1.0, 10 μg/ml) stimulate LH release suggests that the effect of ETYA cannot be explained by an action on cyclooxygenase. The action of ETYA may be mediated either via an effect on lipoxygenase or through some nonspecific action (such as altered membrane fluidity).     

Release and specific binding of prostaglandins in bovine pineal gland

Incubated bovine pineal glands released prostaglandin E- and prostaglandin F-like material (304 ± 20 and 582 ± 56 pg/mg dry tissue wt/h, respectively) and the release was increased 2.2 2.9-fold by adding 10⁻⁴–10⁻⁶M of norepinephrine to the medium. Binding assays revealed the existence of high affinity binding of ³H-prostaglandin E₂ (³H-PGE₂) and ³H-prostaglandin F_2α (³H-PGF_2α) in low speed supernatants of pineal homogenates. Binding was increased by increasing Ca⁺⁺ concentration in medium up to 2 mM, was heat-labile and was depressed following incubation with trypsin. In subcellular fractionation studies maximal ³H-PG binding was found in the 27000 × g pellet. Scatchard analysis of ³H-PGE₂ binding revealed the presence of a single population of binding sites with a K_d= 1.2 nM and a binding site concentration of 1–2 pmoles/g protein. A single population of binding sites for ³H-PGF_2α was also detected with a K_d= 1.7 nM and a similar binding site concentration. Non-radioactive PGE₁ and PGE₂ were almost equally effective to compete for ³H-PGE₂ binding sites (ED₅₀= 5 and 2 nM, respectively). Unlabeled PGF₂ was relatively ineffective to compete for ³H-PGE₂ binding (ED₅₀>1000 nM) but displaced effectively ³H-PGF_2α binding (ED₅₀= 1.2 nM).     

Antagonistic effect of enterocin CCM 4231 from Enterococcus faecium on “bryndza”, a traditional Slovak dairy product from sheep milk

“Bryndza” is a traditional Slovak dairy product (type of soft cheese) made from sheep cheese which was ripened for 14 days. Because its manufacture, transporting and/or storing represent conditions which facilitate contamination, the effect of enterocin CCM4231 in “bryndza” was investigated with the aim to reduce the contaminant agents. “Bryndza” was divided into equal portions (50 g). The experimental sample (ES) as well as the control sample one (C1) were inoculated with Listeria innocua Li1 strain. The other control samples C2 and C3 were without Li1 strain. C3 control was selected as a reference control. ES and C2 portions were treated with purified enterocin CCM4231 in a concentration of 6400 AU/ml. Before the experimental inoculation, “bryndza” was checked for the presence of contaminant agents. The experiment lasted 1 week and the samples were stored in the refrigerator at 4 °C. Sampling was performed on day 1, on day 4 and on day 7. The control samples C2 and C3 were checked only on day 1 and then after 1 week. The following contaminant agents were detected in “bryndza” before its experimental inoculation with L. innocua Li1 strain: Escherichia coli in the amount 10³ cfu/ml/g, Staphylococcus aureus (10² cfu/ml/g) and enterococci (10⁴ cfu/ml/g). In the control sample C2, the number of E. coli was reduced to 10² cfu/ml/g. Enterococci and staphylococci were totally eliminated there. Concerning C3 control, natural decrease of bacteria was found and/or their unchanged counts. The value of pH (5) was stable during the whole experiment. In the experimental sample inoculated with Li1 strain, its counts were decreased immediately after enterocin CCM4231 addition approximately by one order of magnitude. This inhibitory effect was also detectable on day 4 by the difference of one order of magnitude between ES and C1. On day 7, 10³ cfu/ml/g of Li1 strain were detected in both samples (ES, C1). The difference by one order of magnitude indicated, an inhibitory effect of enterocin CCM4231 in “bryndza”. However, bacteriocin activity was not determined by laboratory analyses.     

(4S)-4-amino-5,6-heptadienoic acid (MDL 72483): A potent anticonvulsant GABA-T inhibitor

(4S)-4-Amino-5,6-heptadienoic acid ((S)--allenyl-GABA; MDL 72483) is a potent inactivator of brain GABA-T in mice; (ED₅₀ (i.p.)=60 mg·kg^–1; ED₅₀ (oral)=70 mg·kg^–1). Its anticonvulsant effects against 3-mercaptopropionic acid (MPA)-induced seizures in mice is related to the elevation of whole brain GABA concentrations: The mentioned doses of MDL 72483 which cause a decrease of GABA-T activity by 50%, produce within 5 h after dosing an increase of GABA concentration by about 3 mol·g^–1, and protect 50% of the mice against seizures in this model of presynaptic GABA deficit. When given orally MDL 72483 is about five times more potent than vigabatrin ((4R/S)-4-amino-5-hexenoic acid) a known antiepileptic GABA-T inhibitor. Complete protection was achieved with a dose of 150 mg·kg^–1. Similar to vigabatrin, MDL 72483 does not protect significantly against metrazol-induced convulsions. However, at a dose of 300 mg·kg^–1, the time elapsing between metrazol administration and onset of convulsions was prolonged by a factor of 3.4. Oral administration of MDL 72483 for up to 19 days at a daily dose of 91–96 mg·kg^–1 did not produce any obvious behavioral changes in mice, nor was the ED₅₀ of the drug in MPA-seizure tests significantly altered by the pretreatment. These observations indicate that MDL 72483 is a promising drug for the treatment of certain epilepsies.Special issue dedicated to Dr. Eugene Roberts.     

Immunogenicity of Plague Vaccines in Mice and Guinea Pigs

The median effective doses (ED₅₀) of 28 lots of killed Pasteurella pestis strain 195/P vaccine were determined in mice and guinea pigs. Mice were injected with vaccine alone, whereas guinea pigs received vaccine suspended in incomplete Freund's adjuvant. Potency ratios of vaccines were obtained by comparing the ED₅₀ of the test with that of a reference vaccine. Mean potency ratios of 1.82 ± 0.50 in mice and 3.22 ± 0.56 in guinea pigs were obtained, and the difference between these means was significant, P = <0.01. The number of organisms in the challenge dose did not significantly affect the ED₅₀ of a vaccine in guinea pigs. However, irrespective of vaccinating route, nearly 1,000 times as much vaccine was required in the absence of adjuvant as in its presence to produce comparable protective indexes in the guinea pig. The response of guinea pigs did not offer any improvement over mice in evaluating the efficacy of plague vaccines.     

Effect of Some Pesticides on Reproduction of Rotifer <Emphasis Type="Italic">Brachionus plicatilis</Emphasis> Müller

Pesticides have been major contributors to environmental pollution and they are now widely distributed in aquatic environments. Zooplankters are frequently used as test animals to detect aquatic contaminants because of their sensitivity and ecological importance. We investigated the effect of a 7-day exposure to four commonly used pesticides (diazinon, fenitrothion, methoprene and isoprothiolane) on reproduction of the rotifer Brachionus plicatilis. Pesticide concentrations of 3–7 times lower than the 24-h 50% lethal concentration (24-h LC₅₀) were tested to determine the ‚no observed effect’ concentration (NOEC), ‚lowest observed effect’ concentration (LOEC), and the ‚50% effective’ concentration (EC₅₀) on specific growth rate (r), sexual reproduction, fertilization, resting egg production, and hatchability of resting eggs. Results showed that the lowest EC₅₀ value of r, mixis, fertilization, and resting egg production of 1.4 μM for diazinon was 63 times lower than its 24-h LC₅₀ of 88.4 μM, while for fenitrothion it was 66 times (3.5 and 229.8 μM, respectively). For isoprothiolane, the lowest EC₅₀ value of r, mixis, fertilization, and resting egg production of 8.9 μM was 25 times lower than its 24-h LC₅₀ of 220.7 μM, while for methoprene was 37 times (2.7 and 100.8 μM, respectively). In all pesticides, hatching rate of resting eggs consistently gave the lowest EC₅₀ values which is about 2–40 times lower than the lowest EC₅₀ of r, mixis, fertilization, and resting egg production. Hatchability of resting eggs therefore is the most sensitive parameter in detecting effects of pesticides exposure in rotifer B. plicatilis.     

JM-1232(−) and propofol,a new combination of hypnotics with short-acting and non-cumulative preferable properties

Drug interactions are significant in anesthesiology because drug combinations can potentially possess novel properties. The pharmacological advantages of a new combination of the benzodiazepine receptor agonist JM-1232(−) and propofol were investigated in mice. Male adult mice were administered JM-1232(−) or propofol or combinations of the two drugs intravenously. Loss of the righting reflex was evaluated as achieving hypnosis, and the time until recovery of the reflex was measured as hypnosis time. After determining the ED₅₀, doses double and triple the ED₅₀ of propofol were injected with JM-1232(−) to compare hypnosis time. The injections were repeated four times, and the hypnosis times were compared. Flumazenil was administered separately immediately after the last dose was injected. The ED₅₀ values ([95% confidence interval]) for hypnosis were 3.76 [3.36–4.10] for JM-1232(−) and 9.88 [8.03–11.58] mg kg⁻¹ for propofol. Co-administration of 0.5 and 1 mg kg⁻¹ JM-1232(−) reduced the ED₅₀ values of propofol to 1.76 [1.21–2.51] and 1.00 [0.46–1.86] mg kg⁻¹, respectively. The drug combination for hypnosis produced a supra-additive interaction. Hypnosis time was significantly shorter in the groups given the mixtures compared to each hypnotic administered alone. After repeated injections, hypnosis time with the mixtures showed smaller prolongation than that with the hypnotic alone. Flumazenil completely restored the recovery time after anesthesia. The combination of JM-1232(−) and propofol showed a supra-additive interaction, and the reduced hypnotic dose contributed to a faster recovery even after multiple injections.     

Anti-Analgesic Effect of the Mu/Delta Opioid Receptor Heteromer Revealed by Ligand-Biased Antagonism

Delta (DOR) and mu opioid receptors (MOR) can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED₅₀ for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED₅₀ had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED₅₀ for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment.     

Effects of epinephrine, glucagon and vasoactive intestinal polypeptide on chloride secretion by teleost opercular membrane

Summary The effects of epinephrine, glucagon and vasoactive intestinal polypeptide on chloride secretion by chloride cell-containing isolated opercular membranes from the seawater-adapted euryhaline teleost, the tilapiaSarotherodon mossambicus, have been examined. Epinephrine inhibits chloride secretion, measured as the short-circuit current (I _sc), via -receptors, in a dose-dependent fashion. The minimum effective dose is 10^–9 M, ED₅₀ equals 2×10^–7 M and maximal inhibition at 10^–5 M is nearly 80%. Inhibition of phosphodiesterase by isobutylmethylxanthine (IBMX; 10^–4 M), does not alterI _sc in untreated tissues, but it completely reverses the epinephrine inhibition ofI _sc, suggesting that hormones which modulate cAMP in chloride cells may alter chloride secretion. Glucagon and vasoactive intestinal polypeptide also stimulateI _sc in epinephrine-inhibited tissues, an effect potentiated by IBMX. The effect of glucagon is dose-dependent with a minimum effective dose of 10^–9 M, ED₅₀ equal to 8×10^–8 M and a maximum stimulation of 72% at 10^–5 M.Analysis of the effects of epinephrine and IBMX onI _sc and tissue conductance suggests that these agents act antagonistically on a nonconductive transport mechanism. It is proposed that IBMX and hormones which increase intracellular cAMP levels stimulate chloride secretion in epinephrine-inhibited tissues by stimulating a neutral sodium chloride cellular entry-step mechanism.Abbreviations ED ₅₀ effective dose causing half-maximal inhibition or stimulation - IBMX isobutylmethylxanthine - VIP vasoactive intestinal polypeptide     

Inhibition of muscarinic receptor-mediated Ca27#x002B; mobilization by phorbol 12-myristate 13-acetate in chick embryo cells

Summary A muscarinic cholinergic receptor is present on undifferentiated cells of the chick embryo. Stimulation of the muscarinic receptor with muscarinic agonists triggers intracellular Ca^2#x002B; mobilization. Here, we investigate the effect of phorbol 12-myristate 13-acetate (PMA) on the muscarinic receptor-mediated Ca^2#x002B; mobilization, which is monitored in cell suspensions of chick embryos of stage 24 by chlorotetracycline fluorescence. PMA inhibits the Ca^2#x002B; mobilization in a time-dependent and concentration-dependent manner without changing the ED₅₀ of acetylcholine. The concentration of PMA that gives halfmaximal inhibition is 3.1×10^–9 M PMA.     

Green Fluorescent Protein-labeled Recombinant Fluobody for Detecting the Picloram Herbicide

A green fluorescent protein-labeled fluobody was designed to develop a simple immunoassay method for detecting picloram herbicide in an environmental sample. The gfp gene was successfully inserted into the pSJF2 vector harboring the picloram-specific antibody fragment to yield pSJF2GFP. Picloram spiking in an environmental river sample could be indirectly detected by observing the fluorescence intensity value of the gfp-fluobody, exhibiting specific sensitivity to free picloram with an IC₅₀ value of 50 ppb. Using the gfp-fluobody immunoassay avoids the enzyme-substrate reaction for calorimetric detection that is required in an enzyme-linked immunosorbent assay (ELISA).     

A BASIC computer program for calculation of photosynthesis,stomatal conductance,and related parameters in an open gas exchange system

Computer programs written in BASICA (IBM'S VERSION OF BASIC) language were developed for the calculation of the gas exchange parameters of CO₂ assimilation, leaf conductance, stomatal conductance, residual conductance, intercellular CO₂ concentration, transpiration, water use efficiency and transpiration ratio in an open system. Formulas are discussed in both an algebraic and in a BASIC computer program form. Calculations based on mole fractions of CO₂ and water vapor are explained and both molar and mass fluxes are included in the program output to facilitate comparisons with data from the literature. Corrections are made in the program to account for under-estimation of CO₂ assimilation due to the increase in flow rates out of sample chambers caused by simultaneous transpiration. A sample output is included to illustrate the formatting capability of the program.Michigan Agricultural Experiment Station Journal Article No. 11576.Michigan Agricultural Experiment Station Journal Article No. 11576.     

Antiabortifacient action of dibenzyloxyindanpropionic acid in mice

DIPA [5,6-bis(dibenzyloxy)-1-oxo-2-propyl-2-indanpropionic acid] was evaluated for its antiabortifacient action in mice. PGF_2α administered intramuscularly twice daily at 525 μg/kg per dose starting on day-17 of gestation resulted in premature delivery (prior to day-19 of gestation) in 55% of the animals. This constituted an ED₅₀ abortifacient dosage schedule of PGF_2α. Intramuscular administration of DIPA at a dose of 50 mg/kg twice daily, starting on day-15 of gestation, protected the mice against the premature delivery induced by the ED₅₀ dosage schedule of PGF_2α in that only 20% of the animals delivered prematurely. In saline-treated controls, none of the animals delivered prior to day-19 of gestation. Thus, DIPA appears to be an effective antiabortifacient agent.     

An enzyme-linked immunosorbent assay for 6-keto PGF

An enzyme-linked immunosorbent assay for 6-keto prostaglandin F_1α, a stable metabolite of prostacyclin, has been developed. The assay allows quantitation of 6-keto PGF_1α in the range 1–200 pg/0.1 ml and shows very low cross reactivity to nine other prostaglandins. Dose dependent stimulation by thrombin of 6-keto PGF_1α formation in human endothelial cells in culture has been used to verify the assay. Quantitation by the enzyme linked immunosorbent assay agrees closely with determination by radioimmunoassay.