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Postnatal development of methionine-enkephalin modulation of cholinergic transmission in cat ileum.

The age-dependent effects of methionine-enkephalin (Met-enk) on contractions and [3H]-acetylcholine ([3H]-ACh) release evoked by electrical field stimulation (EFS) were studied in vitro on cat terminal ileum of young (2-month old) and adult cats. Radioactivity was measured by liquid scintillation spectrometry and the effect of Met-enk was evaluated by the FrS2/FrS1 ratio. Scopolamine, 1 microM, abolished the EFS-induced contractions. Met-enk dose dependently (0.01-1 microM) decreased the EFS-induced contractions. The inhibitory effect of Met-enk on the evoked contractions was more pronounced in adult cats compared to that in young cats. In adult animals Met-enk, 1 microM, almost completely inhibited the evoked contractions (94.6 +/- 2.6% of inhibition) while in the young cats its inhibitory effect was less pronounced (52.1 +/- 6.8%). Met-enk decreased the EFS-evoked release of [3H]-ACh by 44.6 +/- 4.6% in adult cats and by 21.6 +/- 1.6% in young cats. The data suggest opioid modulation of cholinergic transmission in cat terminal ileum at neuronal level occurring as early as the postnatal period and increasing with the ontogenesis.

Acetylcholine↗

Allergens of mammalian origin. IV. Evidence for common allergens in cat and dog serum.

IgE antibodies present in serum from 3 patients clinically sensitive to cat and dog were shown to combine with whole cat and dog sera linked to cellulose particles. Employing a modified radioallergosorbent technique (RAST), it was shown that cat and dog sera inhibited the binding of IgE antibodies to insolubilized cat serum and to insolubilized dog serum. These findings suggest that cat and dog sera have common allergens. Other mammalian sera were also tested and found to have little inhibitory activity. Cat and dog sera did not inhibit the binding of IgE antiragweed antibodies to an insolubilized ragweed fraction. Following separation of cat serum by gel filtration on Sephadex G-200 or electrophoresis in acrylamide gel, several fractions were found to inhibit the binding of IgE antibodies to insolubilized cat and dog sera. Whether the heterogeneity observed reflects the presence of single allergens with diverse size and charge properties or multiple allergens remains to be determined.

Allergens↗

Safety and efficacy of oral immunotherapy with standardized cat extract.

Fifty-three subjects with positive skin prick test results to cat extract and rhinoconjunctival symptoms on exposure to cat dander were enrolled in a double-blind, placebo-controlled study of oral cat immunotherapy. Responses were assessed by development of symptoms and nasal blockage on exposure to an apartment contaminated with cat dander, by titrated skin prick tests, and by cat-specific IgG and IgE. A total cumulative dose of 2.5 x 10(6) allergy units or 436 U Fel d I were administered over a period of 3 months. Both groups of subjects had significantly fewer symptoms on exposure to cat dander during the course of the study, but there was no significant difference between active and placebo groups. There were no significant changes in either group in nasal blockage, skin prick test results, or specific IgG levels. Both groups had significant increases in cat-specific IgE, but there were no differences between groups. Subjects receiving active treatment had a slight excess of gastrointestinal complaints. Two subjects receiving active treatment experienced systemic symptoms: one had pulmonary edema, and the other had persistent asthma and urticaria, which may have represented reactions to the treatment. We conclude that oral cat immunotherapy with the preparation and doses used in this study is not effective.

Administration, Oral↗

Identification of the sympathetic preganglionic pathway to the cat stellate ganglion.

Both intraspinal and segmental preganglionic pathways to sympathetic ganglia have been proposed based on different methods of horseradish peroxidase application. The present study mapped the projections of preganglionic neurons to the stellate ganglion in the cat by horseradish peroxidase injection into ganglia with various white rami intact. Central and peripheral cut ends of the severed white rami were tied to eliminate leakage of peroxidase from the ganglia. In control cats with all white rami intact, an average of 9186 neurons were labeled in the spinal cord ipsilateral to the injection from C8 to T9; the highest density of labeling occurred in the first and second thoracic segments. In cats with single white rami intact (T1, T2, or T3), neurons were labeled only in the spinal cord segment that corresponded to the intact ramus and one segment rostral to it. In additional experiments, the spinal cord was hemisected a few segments below, and ipsilateral to the injected ganglion with all rami intact. In these cats neurons were labeled with a similar distribution to control cats, indicating that the preganglionic pathway was extraspinal. Finally, experiments were performed on cats with a single ramus intact, but without ligatures around the cut rami. The distribution of neuronal labeling was similar to control cats (labeled cells from C8 to T9). These results demonstrate that peroxidase leakage from the stellate ganglion can result in an artifactual labeling which would indicate an intraspinal preganglionic pathway. Thus, the present experiments support a segmental distribution of upper thoracic sympathetic preganglionic neurons to the stellate ganglion in the cat, and do not provide evidence for long intraspinal pathways of preganglionic neurons before exit from the cord.

Animals↗

Pilot study of the effect of acemannan in cats infected with feline immunodeficiency virus.

Acemannan, a complex carbohydrate shown to stimulate interleukin-1, tumor necrosis factor alpha and prostaglandin E2 production by macrophages, has also demonstrated antiviral activity in vitro against human immunodeficiency virus, Newcastle disease virus and influenza virus. A pilot study was undertaken to determine acemannan's effect in 49 feline immunodeficiency virus (FIV) infected cats with clinical signs of disease (Stage 3, 4 or 5), 23 of which had severe lymphopenia. Cats received acemannan either by intravenous (Group 1) or subcutaneous (Group 2) injection once weekly for 12 weeks, or by daily oral (Group 3) administration for 12 weeks. Upon entry into the study, cats were randomly assigned to one of the three groups. Laboratory analyses were performed at the beginning of the study and at Weeks 6 and 12. Cats were allowed to continue with a predetermined maintenance regimen of acemannan after completing the 12-week study. Thirteen cats died during the course of treatment. Upon necropsy, the most frequent histopathologic findings were neoplastic, kidney and pancreatic disease. Friedman's two-way ANOVA test showed no significant differences in efficacy among groups administered acemannan by the different routes. Therefore, groups were combined and a signed-ranks test was used to determine changes over time. A significant increase was seen in lymphocyte counts (P < 0.001). Neutrophil counts decreased significantly (P = 0.007), as did incidence of sepsis (P = 0.008). When cats entering with lymphopenia were analyzed separately, a much greater increase in lymphocyte counts was noted (235%) compared with non-lymphopenic cats (42%). A survival rate of 75% was found for all three groups. Thirty-six of 49 animals are alive 5-19 months post-entry. These results suggest that acemannan therapy may be of significant benefit in FIV-infected cats exhibiting clinical signs of disease.

Animals↗

Delayed hypersensitivity testing as a clinical measure of cell-mediated immunity in the cat.

The purposes of this study were to examine the cell-mediated immune response of the normal cat to the modified live feline viral rhinitis, calicivirus, and parvovirus (FVRCP) vaccine (Felocell CVR, Norden, Lincoln, NE), and to evaluate the intradermal skin test as a clinical measure of the immune response of cats. Vaccine and diluent were injected intradermally on the dorsal pinna of 34 normal adult cats. Skin thickness measurements, lymphocyte counts, and Concanavalin A mitogenesis indices were evaluated in 18 of these cats. Skin biopsies were obtained in 16 cats. In normal cats, the FVRCP vaccine induced a delayed hypersensitivity response characterized by a mononuclear infiltrate most pronounced at 72 h. Five cats with either feline leukemia (FeLV) or feline immunodeficiency virus (FIV) were tested and had a significantly reduced response to the skin test. The skin test provides a clinically useful method of evaluating immune function in cats and may be useful in development of a prognostic index.

Animals↗

Tumor necrosis factor-alpha responses are depressed and interleukin-6 responses unaltered in feline immunodeficiency virus infected cats.

Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, causes an acquired immunodeficiency syndrome in cats. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV is associated with dysregulation of the cytokine network. While alterations in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression have been reported in HIV-infected patients, changes attributable to HIV and those caused by cofactors such as secondary infections cannot always be readily distinguished. This study evaluated the effect of FIV infection on TNF-alpha and IL-6 production in cats not exposed to other potential cofactors such as secondary infections. TNF-alpha and IL-6 activities were evaluated in bronchoalveolar lavage (BAL) cells from FIV-infected and uninfected specific pathogen free (SPF) cats. Supernatants from lipopolysaccharide (LPS)-stimulated BAL cells from uninfected SPF cats had high levels of TNF-alpha and IL-6 activity, while stimulated BAL cell supernatants from FIV-infected SPF cats had significantly lower levels of TNF-alpha but unaltered IL-6 activity. Similarly, Con A/phorbol myristate acetate (PMA) stimulated non-adherent (NA-) peripheral blood mononuclear cells (PBMC) from FIV infected cats synthesized less TNF-alpha than similarly treated NA-PBMC from uninfected cats. Feline immunodeficiency virus could be recovered from the culture supernatants of BAL cells from infected cats by co-cultivation with susceptible lymphocytes. In situ hybridization identified FIV mRNA in a small fraction of alveolar macrophages in the BAL cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Few neocortial and thalamic morphological changes after a neonatal frontal cortical ablation contrast with the effects of a similar lesion in fetal cats.

To further understand the neuroanatomical consequences following perinatal brain injury, quantitative morphometric analysis was performed on the brain of cats receiving a unilateral frontal cortical ablation between postnatal days (P) 9 and P 14 and intact control cats. In all cats, the volume of the neocortex and thalamus was measured bilaterally and that of the thalamic ventrobasal complex (VBc) was measured ipsilaterally. In addition, using stereology, the neuronal and glial (presumably) cell packing densities (CPD) and the total number of neurons and glial cells (TCN) were measured in the ipsilateral VBc. The neuronal and glial cell cross-sectional areas (CSA) were also measured in the ipsilateral VBc. The mean ipsilateral and contralateral neocortex volumes were similar between the two animal groups. There was a statistically significant 14% and 13% reduction in mean ipsilateral and contralateral thalamic volumes, respectively for the lesioned animals, while the VBc shrank by 16% relative to intact controls. The mean neuronal and glial CPD were similar between the two groups. The mean neuronal TCN was reduced by 10% in the neonatal-lesioned cats, while the mean glial TCN was reduced by 31% in the same animals, however neither value reached significance. Lastly, the mean CSA of neurons and glial cells showed a tendency to be smaller in the lesioned cats by 8% and 9%, respectively. These results: (a) indicate that the neonatal lesion caused only minor morphological brain alterations and this sharply contrast with the marked changes previously reported in cats with a similar lesion sustained prenatally; (b) suggest that the enhanced behavioral recovery and/or sparing reported for the present cats compared to fetal-lesioned animals is at least partially due to the morphological sparing reported here; (c) together with previous findings in fetal cats, support the hypothesis that the morphological changes after a neonatal neocortical lesion are qualitatively different and may depend on different mechanisms as compared to those occurring after similar damage sustained prenatally.

Animals↗

Loss of object discrimination after ablation of the superior colliculus-pretectum in binocularly deprived cats.

The effects of ablation of the superior colliculus-pretectum on a previously elaborated object discrimination task were compared in cats reared in normal conditions, in cats reared in the laboratory, and in cats deprived of patterned vision. The normally reared cats were least deficient postoperatively, whereas deprived cats were most deficient. Seven of 8 deprived cats failed to re-reach criterion. Previous results showed that after removal of the visual cortex deprived cats were less deficient than normally reared controls. It is concluded that in discrimination learning the function of the abnormal visual cortex of deprived cats is partially taken over by the superior colliculus-pretectum.

Animals↗

Single and combined lesions of the cats thalamic mediodorsal nucleus and the mamillary bodies lead to severe deficits in the acquisition of an alternation task.

The acquisition of a spatial alternation task was tested in five groups of adult cats. Two groups were used for control; one of them consisted of nonlesioned cats, the other of cats with chemical lesions (ibotenic acid) of the ventral tegmental area. The other three groups of cats received chemical lesions of the mediodorsal nucleus of the thalamus, the mamillary bodies, or of both structures together. Cats with lesions of the ventral tegmental area were non-significantly impaired in comparison to non-lesioned cats in the acquisition of the task. Cats with lesions of the mediodorsal nucleus, the mamillary bodies, or with combined lesions of both structures were significantly impaired, compared to the two control groups; among each other, however, their performance rates were similar. As none of the cats with single or combined lesions of the mamillary and the mediodorsal nuclei manifested observable abnormalities with respect to motor, motivational, or emotional behavior during their testing period, it is concluded that their--compared to the other two groups--inferior performance was due to a memory defect. As all three kinds of lesions resulted in a similar defect, it is suggested that the mamillary and the mediodorsal nuclei transmit information to one or more common target area(s), which is (are) dependent on information from either nucleus to operate effectively.

Animals↗

Sensory, motor and cognitive alterations in aged cats.

These experiments were designed to assess some of the sensory, motor and cognitive alterations that occur in aged cats. Three groups of cats (1-3, 5-9 and 11-16 years of age) were tested in four behavioral tasks to assess age-dependent changes in locomotor activity, fine motor coordination, reactivity to auditory stimuli and spatial reversal learning. In tests of locomotor activity, 11-16 year old cats displayed altered patterns of habituation compared to 1-3 and 5-9 year cats. There were no decrements in fine motor coordination in the 11-16 year cats as measured by their ability to traverse planks of varying width or by their scores on a neurological examination. The 11-16 and 5-9 year cats both displayed increased reactivity to auditory stimuli. On tests of spatial reversal learning, 11-16 year cats displayed superior performance compared to 5-9 or 1-3 year animals, making fewer errors and requiring fewer trials to reach criterion. These findings indicate that a series of age-related behavioral changes occurs in the cat. Some of these may be related to morphological and neurophysiological alterations in neurons in the caudate nucleus.

Aging↗

Cat-P300 present after association cortex ablation.

The cat-P300 is a positive endogenous potential, larger to a stimulus when rare than when frequent, with a latency of 200-500 msec. The role of polysensory association cortex, postulated to be important in human P300 generation, was assessed in the cat. EEG was recorded in 13 awake cats from a skull screw at the vertex. Stimuli included frequent (P = 0.80) 1 kHz and rare (P = 0.10) 2 kHz tone pulses with probabilities counterbalanced across 260-trial blocks. After 12 preoperative sessions, bilateral ablations were made of pericruciate cortex (4 cats), anterior lateral and medial suprasylvian gyri (4 cats) and all 3 areas (5 cats). Postoperatively, all 13 cats showed a P300 across 12 recording sessions. Thus polysensory association cortex is not essential for generation of the cat-P300.

Acoustic Stimulation↗

Middle and long latency auditory evoked potentials in cat. I. Component definition and dependence on behavioral factors.

Middle (10-50 ms) and long (50-600 ms) latency auditory evoked potentials (AEPs) were investigated in artificially respired, muscle-paralyzed cats. Similarity to human potentials of comparable latencies was examined in two ways: (1) the similarity of waveform features such as peak amplitude, polarity and latency, and (2) the effects of task-related variables on these various waveform features. Four behavioral variations of a classical pupillary conditioning paradigm were used to vary attention and arousal. Twelve peaks and troughs were identified in the AEP: P10, N13, P17, N22, P31, N41, P55, N70, N100, N140, P260 and N520. Principal components analysis (PCA) defined 7 AEP components, some of which spanned several peaks. Analysis both of peak latencies and amplitudes, and of principal component scores, revealed differential effects of the behavioral manipulations on these components: those with latencies longer than 50 ms were strongly influenced by behavioral variations, while earlier components were relatively immune to these effects. On the basis of these findings, several relationships between cat and human AEP components were suggested. Specifically, peaks P10-P41 in the cat were thought related to human middle latency components, cat P55 to human P50, cat N140 to human N300, and cat P260 to human P300. Cat N520 was comparable to several long latency components in humans. No obvious correspondences between cat AEP components and human N90 and P170 were identified.

Acoustic Stimulation↗

Spontaneous rates, thresholds and tuning of auditory-nerve fibers in the gerbil: comparisons to cat data.

Characteristics of 245 auditory nerve fibers in eleven Mongolian gerbils are described in terms of spontaneous rates, thresholds, and tuning curves. The animals were reared in a low-noise environment and had similar hearing thresholds across frequency. Tuning curves were obtained with an algorithm developed to characterize the tuning of auditory fibers in cat, thereby allowing direct comparisons to published data from cat. The results demonstrate that basic similarities exist between gerbil and cat data, although some minor differences are also apparent. Tuning curve bandwidths, as measured 10 and 40 dB above the thresholds at the characteristic frequency (CF), follow trends found in cat data. Like cat, auditory nerve fibers in the gerbil have a range of spontaneous rates. In individual gerbils, fibers associated with low spontaneous rates have higher thresholds than do fibers of similar CF with high rates. Five of the eleven gerbils showed profiles of spontaneous rate across frequency reminiscent of those obtained from quiet-raised young cats. The profiles of the remaining gerbils tended to be compressed to a smaller range of spontaneous rates for characteristic frequencies above about five kHz, much like older cats with unknown noise histories. The cause of the spontaneous compression is not obvious. The correspondence between cat and gerbil with regard to spontaneous rate and CF threshold implies the presence of fundamental mechanisms that are common to mammalian auditory systems.

Action Potentials↗

Effects of caudate nuclei removal in cats. Comparison with effects of frontal cortex ablation.

A method is described for performing one-stage ablation of the caudate nuclei through a midline approach in cats. Ten bilateral acaudate cats (BAc), with an average of 84% of caudate tissue removed, were studied for a average of over 6 months (three, for over 1 year). In addition, 11 cats with unilateral caudectomy (UAc), with an average of 95% of the nucleus removed, 10 cats with bilateral removal of the frontal-cortical areas (BFr), and four sham-operated cats (ShO) were also studied. Most cats were implanted with recording electrodes in neocortical area, the hippocampus, the potine reticular formation, neck muscles, and orbits. The results of the gross behavioral, neurological, and polygraphic observations are reported. 1. A long-lasting, behavioral change labeled "compulsory approaching syndrome" (CAs) was observed following surtery in all BAc cats. This syndrome was characterized by stereotyped, "compulsory," and prolonged approaching or following of persons, cats, or objects apparently aimed at a physical contact with the approached target and persisting under unusual conditions...

Animals↗

Chromosome-scale assembly with improved annotation provides insights into breed-wide genomic structure and diversity in domestic cats.

INTRODUCTION: Comprehensive genomic resources offer insights into biological features, including traits/disease-related genetic loci. The current reference genome assembly for the domestic cat (Felis catus), Felis_Catus_9.0 (felCat9), derived from sequences of the Abyssinian cat, may inadequately represent the general cat population, limiting the extent of deducible genetic variations. OBJECTIVES: The goal was to develop Anicom American Shorthair 1.0 (AnAms1.0), a reference-grade chromosome-scale cat genome assembly. METHODS: In contrast to prior assemblies relying on Abyssinian cat sequences, AnAms1.0 was constructed from the sequences of more popular American Shorthair breed, which is related to more breeds than the Abyssinian cat. By combining advanced genomics technologies, including PacBio long-read sequencing and Hi-C- and optical mapping data-based sequence scaffolding, we compared AnAms1.0 to existing Felidae genome assemblies (20 scaffolds, scaffolds N50&#xa0;>&#xa0;150 Mbp). Homology-based and ab initio gene annotation through Iso-Seq and RNA-Seq was used to identify new coding genes and splice variants. RESULTS: AnAms1.0 demonstrated superior contiguity and accuracy than existing Felidae genome assemblies. Using AnAms1.0, we identified over 1.5 thousand structural variants and 29 million repetitions compared to felCat9. Additionally, we identified > 1,600 novel protein-coding genes. Notably, olfactory receptor structural variants and cardiomyopathy-related variants were identified. CONCLUSION: AnAms1.0 facilitates the discovery of novel genes related to normal and disease phenotypes in domestic cats. The analyzed data are publicly accessible on Cats-I (https://cat.annotation.jp/), which we established as a platform for accumulating and sharing genomic resources to discover novel genetic traits and advance veterinary medicine.

Animals↗

Ionotropic glutamate receptor GluR2/3-immunoreactive neurons in the cat, rabbit, and hamster superficial superior colliculus.

Ionotropic glutamate receptor (GluR) subtypes occur in various types of cells in the central nervous system. We studied the distribution of AMPA glutamate receptor subtype GluR2/3 in the superficial layers of cat, rabbit, and hamster superior colliculus (SC) with antibody immunocytochemistry and the effect of enucleation on this distribution. Furthermore, we compared this labeling to that of calbindin D28K and parvalbumin. Anti-GluR2/3-immunoreactive (IR) cells formed a dense band of labeled cells within the lower superficial gray layer (SGL) and upper optic layer (OL) in the cat SC. By contrast, GluR2/3-IR cells formed a dense band within the upper OL in the rabbit and within the OL in the hamster SC. Calbindin D28K-IR cells are located in three layers in the SC: one within the zonal layer (ZL) and the upper SGL in all three animals, a second within the lower OL and upper IGL in the cat, within the IGL in the rabbit and within the OL in the hamster, and a third within the deep gray layer (DGL) in all three animals. Many parvalbumin-IR neurons were found within the lower SGL and upper OL. Thus, the GluR2/3-IR band was sandwiched between the first and second layers of calbindin D28K-IR cells in the cat and rabbit SC while the distribution of GluR2/3-IR cells in the hamster matches the second layer of calbindin D28K-IR cells. The patterned distribution of GluR2/3-IR cells overlapped the tier of parvalbumin-IR neurons in cat, but only partially overlapped in hamster and rabbit. Two-color immunofluorescence revealed that more than half (55.1%) of the GluR2/3-IR cells in the hamster SC expressed calbindin D28K. By contrast, only 9.9% of GluR2/3-IR cells expressed calbindin D28K in the cat. Double-labeled cells were not found in the rabbit SC. Some (4.8%) GluR2/3-IR cells in the cat SC also expressed parvalbumin, while no GluR2/3-IR cells in rabbit and hamster SC expressed parvalbumin. In this dense band of GluR2/3, the majority of labeled cells were small to medium-sized round/oval or stellate cells. Immunoreactivity for the GluR2/3 was clearly reduced in the contralateral SC following unilateral enucleation in the hamster. By contrast, enucleation appeared to have had no effect on the GluR2/3 immunoreactivity in the cat and rabbit SC. The results indicate that neurons in the mammalian SC express GluR2/3 in specific layers, which does not correlate with the expression of calbindin D28K and parvalbumin among the animals.

Animals↗

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗