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Background: To determine the efficacy of the Caulis Sargentodoxae prescription, which is an empirical formula of Chinese herbs and has definite curative effects on endometriosis. Methods: The Caulis Sargentodoxae prescription on the growth of ectopic endometria was studied with a rat endometriosis (EMS) model. The EMS model was established by autoplastic transplantation. To study the curative effects of Chinese medicine on EMS in comparison with western medicine, gestrinone and an angiogenesis inhibitor were introduced. The rats were randomly divided into seven groups: normal group, model group, ovariectomized group, gestrinone (western medicine) group, Caulis Sargentodoxae prescription (Chinese medicine) group, apatinib (inhibitor) group, and combination (Chinese medicine + inhibitor) group. After administration for 21 days, the growth inhibitory rates of ectopic endometria in the treatment groups were evaluated, and the levels of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) were detected by ELISA in the serum and peritoneal fluid, as well as in the ectopic endometrial tissues by real-time polymerase chain reaction and Western blotting. Results: The growth inhibitory rates of ectopic endometria in the treatment groups were significantly higher (P < 0.05). In the Caulis Sargentodoxae prescription group, the levels of angiogenesis-related factors, including VEGF and VEGFR2, were reduced in the serum and peritoneal fluid compared with the model group (P < 0.05). In addition, the positive expression of VEGF and VEGFR2 in ectopic endometria significantly decreased in the Caulis Sargentodoxae prescription group both at mRNA and protein levels. Conclusions: VEGF and VEGFR2 levels in the serum and peritoneal fluid can be used as a clinical reference for endometriotic pathogenesis and treatment, and the Caulis Sargentodoxae prescription has reliable therapeutic effects on EMS for its target-action ability to decrease angiogenesis.

Embryo implantation is an essential step for a successful pregnancy, and any defect in this process can lead to a range of pregnancy pathologies. The objective of this study was to explore the role of N-myc downregulated gene 1 (NDRG1) in embryo implantation. It was found that uterine NDRG1 expression has a dynamic pattern during the estrous cycle in nonpregnant mice and that uterine NDRG1 expression was elevated during the implantation process in pregnant mice. The distinct accumulation of NDRG1 protein signals was observed in the primary decidual zone adjacent to the implanting embryo during early pregnancy. Furthermore, uterine NDRG1 expression could be induced by activated implantation or artificial decidualization in mice. Decreased uterine NDRG1 expression was associated with pregnancy loss in mice and was associated with recurrent miscarriages in humans. The in vitro decidualization of both mouse and human endometrial stromal cells (ESCs) was accompanied by increased NDRG1 expression and downregulated NDRG1 expression in ESCs effectively inhibited decidualization. Collectively, these data suggest that NDRG1 plays an important role in decidualization during the implantation process, and the abnormal expression of NDRG1 may be involved in pregnancy loss.

Maternal immune tolerance to the semi-allogenic fetus is required for successful pregnancy in mammals. Monoclonal nonspecific suppressor factor beta (MNSFB) is an immunosuppressive factor present in uterine epithelial and stromal cells, as well as in macrophages and T cells. Although the functional neutralization of MNSFB using specific antibodies against it lead to failed embryo implantation in mice, the exact role of MNSFB at the fetal-maternal interface remains unclear. The present study generated conditional heterozygous Mnsfb-deficient (Mnsfb(+/) (-) ) mice using the LoxP/Cre system. Western-blot analyses showed that uterine MNSFB protein in Mnsfb(+/-) mice was remarkably down-regulated compared to that in the wild-type (Mnsfb(+/+) ) mice. The litter size of female Mnsfb(+/-) mice was significantly reduced, which corresponded to developmental failure of embryos beyond Day 11 of pregnancy. The expression level of MNSFB protein was also lower in the failing compared to the normal embryos. An aberrant interaction between the embryos of Day-4 pregnant wild-type mice and endometrial stromal cells of female Mnsfb(+/-) mice was observed in vitro. The uterine Day-5 abundance of P53, BAX, and BCL-G in pregnant Mnsfb(+/-) mice was significantly decreased compared to that of wild-type mice, whereas the expression of P27 and tumor necrosis factor alpha (TNFA) was elevated. By comparison, the levels of MNSFB and BAX proteins in human decidual tissues obtained from recurrent spontaneous miscarriage patients were significantly reduced compared to those obtained from legal medial abortion, highlighting the involvement of MNSFB in the pathogenesis of recurrent spontaneous miscarriage. Together, these results demonstrated that a deficiency in MNSFb is associated with pregnancy loss, probably through reduced P53 and/or increased TNFA production at the fetal-maternal interface.

Embryo implantation is an essential step for the establishment of pregnancy and dynamically regulated by estrogen and progesterone. NDRG4 (N-myc down-regulated gene 4) is a tumor suppressor that participates in cell survival, tumor invasion and angiogenesis. The objective of this study was to preliminarily explore the role of NDRG4 in embryo implantation. By immunohistochemistry (IHC) and quantitive RT-PCR (qRT-PCR), we found that uterine expression of NDRG4 was increased along with puberal development, and its expression in adult females reached the peak at the estrus stage during the estrus cycle. Furthermore, uterine NDRG4 expression was significantly induced by the treatment of estradiol (E2) both in pre-puberty females and ovariectomized adult females. Uterine expression pattern of NDRG4 during the peri-implantation period in mice was determined by IHC, qRT-PCR and Western blot. It was observed that NDRG4 expression was up-regulated during the implantation process, and its expression level at the implantation sites was significantly higher than that at the inter-implantation sites. Meanwhile, an increased expression in NDRG4 was associated with artificial decidualization as well as the activation of delayed implantation. By qRT-PCR and Western blot, we found that the in vitro decidualization of endometrial stromal cells (ESCs) was accompanied by up-regulation of NDRG4 expression, whereas knockdown of its expression in these cells by siRNA inhibited the decidualization process. In addition, Western blot analysis showed that NDRG4 protein expression was decreased in human villus tissues of recurrent miscarriage (RM) patients compared to normal pregnant women. Collectively, these data suggested that uterine NDRG4 expression could be induced by estrogen, and NDRG4 might play an important role during early pregnancy.

To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii (F. prausnitzii) supernatant on dextran sulfate sodium (DSS) induced colitis in mice.Forty C57BL/6J male mice were randomly divided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score (HDS) was assessed, and plasma interleukin (IL)-17A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt (RORγt) and IL-17A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt mRNA, IL-17A mRNA, and IL-6 mRNA were detected by real-time quantitative polymerase chain reaction (PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter.When compared with the model group, the colon length (P0.05) and body weight (P0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased (P0.05 and P0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17A and IL-6 (P0.05), the protein and mRNA expression of IL-17A and RORγt, and the Th17 cell ratio of spleen cells (P0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group (P0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues.F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL-17A secretion in the plasma and colon mucosa tissues. It can also improve colitis in mice by downregulating IL-6 and prevent colitis by upregulating IL-4.

To investigate the biological significance of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) involvement in oocyte maturation, we screened for proteins that bound to UCH-L1 in mouse ovaries, and we found that the prostate tumor overexpressed-1 (PTOV1) protein was able to bind to UCH-L1. PTOV1 is highly expressed in prostate cancers and considered as a potential marker for carcinogenesis and the progress of prostate cancer. It was reported that PTOV1 plays an important role in cell cycle regulation, but its role in mammalian oocyte development and meiosis is still unclear. In this paper, it was found that the expression levels of PTOV1 in mouse ovaries progressively increased from prepubescence to adulthood. And we found by immunohistochemistry that PTOV1 spreaded in both the cytoplasm and nuclei of oocytes during prepuberty, but in normal adult mouse oocytes, it concentrated not only in nuclei but also on the plasma membrane, though in some oocytes with abnormal shapes, PTOV1 did not display the typical distribution patterns. In granulosa cells, however, it was found to locate in the cytoplasm at all the selected ages. In postnatal mouse ovaries (28 days), estradiol treatment induced the adult-specific distribution pattern of PTOV1 in oocytes. In addition, UCH-L1 was shown to be associated with CDK1, which participated in the regulation of cell cycle and oocyte maturation. Therefore, we propose that the distribution changes of PTOV1 are age-dependent, and significant for mouse oocyte development and maturation. Moreover, the discovery that PTOV1 is associated with UCH-L1 in mouse oocytes supports the explanations for that UCH-L1 is involved in oocyte development and maturation, especially under the regulation of estrogen.

With the increase of mining depth, high-temperature mines have been more and more now; it is about 150 pair mines that have the problem of high-temperature to different extent in china. High-temperature environment directly affects mineworkers in work condition and work efficiency, and is easy to cause insecure behavior and lack of enthusiasm. By investigating thermal source in mine, some surrounding factors that arouse heat hazard are analyzed. The harmfulness to miners in high-temperature environment mostly lies in the destruction of the normal physiological regulation of human body, and the disordering of body's heat balance, such as heat shock, heat cramps and heat exhaustion and so on. The impacts on the safety production in mine include lowering the miner's labor efficiency, easily causing a fire in mine, disordering the mine ventilation system, eroding the equipments and material, resulting in higher accident rates, etc. Finally, by studying evaluation index of heat hazard, the concept of the synthesis-reduced temperature ( SRT ) and its evaluation criteria are put forward, which is a new method for evaluating the degree of heat hazard in high-temperature mine.

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, and oocyte developmental competence is altered in patients with PCOS. In recent years microRNAs (miRNAs) have emerged as important regulators of gene expression, the aim of the study was to study miRNAs expression patterns of cumulus cells from PCOS patients. Methods The study included 20 patients undergoing in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI): 10 diagnosed with PCOS and 10 matching controls. We used deep sequencing technology to identify the miRNAs differentially expressed in the cumulus cells of PCOS. Results There were 17 differentially expressed miRNAs in PCOS cumulus cells, including 10 miRNAs increase and 7 miRNAs decrease. These miRNAs were predicted to target a large set of genes with different functions, including Wnt- and MAPK- signaling pathways, oocyte meiosis, progesterone-mediated oocyte maturation and cell cycle. Unsupervised hierarchical clustering analysis demonstrated that there was a specific miRNAs expression pattern in PCOS cumulus cells. Conclusion We found that the miRNAs expression profile was different in cumulus cells isolated from PCOS patients compared with control. This study provided new evidence for understanding the pathogenesis of PCOS.

Metastasis is one of the hallmarks of cancer malignancy that usually causes more detrimental effects than a primary tumor. Many microRNAs were reported to be involved in the process of tumor metastasis. Hep11 and Hep12 cells were derived from primary and recurrence (intrahepatic metastatic) sites of hepatocellular carcinoma (HCC), respectively. Hep12 exhibited a higher invasive and migratory potential than Hep11. There was also a significantly higher expression of miR-9 in Hep12 cells than in Hep11 cells. Further studies in HCC cell lines demonstrated that miR-9 could promote tumor cell migration and invasion. In addition, miR-9 downregulated KLF17 protein expression by targeting the 3'UTR region of the KLF17 gene directly. As a transcription factor, KLF17 directly acted on the promoters of EMT-related genes (ZO-1, Vimentin and Fibronectin (FN)) in HCC cell lines. Therefore, we conclude that miR-9 may possibly promote HCC migration and invasion through regulation of KLF17.

This study examined the mttuence of human high density ltpoproteins (HDL) on the intracellular free calcium of cultured bovine aortic endothelial cells (BAECs). Intracellular Ca 2+ concentration ([Ca 2+ ] i ) was determined by a fluorescent calcium indicator, Fura-2. It was found that, in the presence of 1 mmol/L extracellular calcium, HDL resulted in a biphasic elevation of [Ca 2+ ] i in BAECs, consisting of an initial, transient component followed by a lower, but more sustained component. Doses of HDL from 25 to 200 μg protein/ml induced marked concentration-dependent elevations of [Ca 2+ ] i in BAECs. The sustained component was abolished by deprivation of extracellular calcium or by pretreatment of endothelial cells with a calcium influx blocker, NiCl 2 . HDL-induced elevation of [Ca 2+ ] i was attenuated in a concentration-dependent way by an inhibitor of calcium release, tetracaine. Repeated applications of HDL (100 μg protein/ml) markedly blunted the initial peak component of the calcium transient of BAECs. These results demonstrate that both intracellular and extracellular calcium pools are responsible for the biphasic elevation of [Ca 2+ ] i induced by HDL in cultured BAECs.

Our research aimed to evaluate the effect of endometriosis on folliculogenesis and pregnancy, and to assess the involvement of inflammatory factors (IL1b, PGE2, PGF2α, and TGFβ2) in follicular fluid. A total of 65 follicular fluid aspirates were collected. Concentrations of inflammatory factors (IL1b, PGE2, PGF2α, and TGFβ2) and steroid hormones (E2, progesterone, FSH, and LH) within follicular fluid as well as serum E2 and LH concentrations were measured. The mRNA expression of IL1b, Ptgs2, aromatase, and PPARγ in granulosa cells was determined. The outcome of ART was monitored and recorded. The oocyte retrieval, rate of metaphase II oocyte, cleavage rate, effective embryo rate, and pregnancy rates of patients with endometriosis were all significantly lower than those of the control patients. In those with endometriosis, serum E2 concentrations were lower than those observed in controls. Aromatase levels in the granulosa cells of the endometriosis group were lower while concentrations of PGE2 in follicular fluid were higher than in the control group. Concentrations of PGE2, PGF2α, TGFβ2, and IL1b were significantly correlated with each other. These results suggest that the outcomes of ART, in relation to serum E2 concentration, were adversely affected by the presence of endometriosis. Furthermore, the results supported that, among the endocrine and inflammatory factors, PGE2 within the follicular fluid impairs the number and quality of oocytes.

To investigate the correlation of endocrine gland-derived vascular endothelial growth factor (EG-VEGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-β1) with the corresponding reproductive outcome in patients who received in vitro fertilization-embryo transfer (IVF-ET).Sixty-seven women undergoing IVF-ET at a university tertiary hospital were recruited for a prospective study. Concentrations of EG-VEGF, VEGF and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA) in follicular fluid (FF) collected during oocyte retrieval (OR) and in serum collected 2 days after OR.In FF, concentrations of both EG-VEGF and VEGF were negatively correlated with peak E2 and the number of MII oocytes retrieved, and positively correlated with each other. In serum, concentrations of all the three growth factors were positively correlated with the rate of good quality embryo, and with one another. Patients in the pregnancy group had lower peak E2 concentrations and higher serum EG-VEGF concentrations than those in the non-pregnancy group, but such tendency was not observed in the case of VEGF and TGF-β1.Both concentrations of EG-VEGF and VEGF in FF were negatively correlated with ovarian response and oocyte maturation. Concentrations of all the three growth factors in serum were positively correlated with embryo quality, but only serum concentrations of EG-VEGF were associated with the pregnancy outcome.

Osteosarcoma is one of the most prevalent primary bone tumors. The pathogenesis and molecular development of this tumor remains elusive. The prognosis is unfavorable due to lack of effective treatment methods. Recent advances in the epigenetics have brought a profound impact on the understanding of molecular mechanisms that lead to osteosarcoma. In this review, we summarized the current literature on epigenetic changes that are thought to contribute to the carcinogenesis of osteosarcoma, and discussed the potential diagnostic and therapeutic applications as well as future areas of research.

Background The study was conducted to investigate the inhibitory effect of 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in mice with a view to identifying whether it might be a suitable agent for postcoital contraception. Study Design The anti-implantation efficacy of AEBSF was determined by counting the number of visible implanted embryos on Day 8 of pregnancy following a single intrauterine injection of AEBSF at doses of 30, 300 and 3000 μg per mouse uterine horn on Day 3 of pregnancy. The reversibility of the inhibitory effect of AEBSF on implantation was further evaluated by observing the outcome of a subsequent pregnancy without AEBSF treatment. Results A dose-dependent inhibitory effect of AEBSF on embryo implantation in vivo was observed. Morphological analysis revealed no significant cytotoxicity of AEBSF on the mouse uterine epithelia. Furthermore, the anti-implantation effect of AEBSF was reversible. Conclusion Intrauterine administration of AEBSF at an appropriate dose might provide a basis for the development of novel contraception.

To investigate the effect of aspirin on the apoptosis of cultured bovine aortic endothelial cells (BAEC) and the signal pathways involved in this process.BAEC were cultured and passaged in Dulbecco's modified Eagle's medium culture medium. Morphologic changes and quantification of apoptotic cells were determined using fluorescence microscope after staining the cells with Hoechst 33258. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) method. DNA fragmentation was visualized by agarose gel electrophoresis. Phospho-p38 mitogen-activated protein kinase (MAPK) expression was detected by Western blotting.Aspirin at low concentrations from 1X10( -10) mol/L to 1X10( -8) mol/L decreased the apoptosis and p38 MAPK phosphorylation induced by H2O2 in BAEC, while high doses of aspirin (1X10( -7)-1X10( -4) mol/L) induced typical apoptotic changes in BAEC and stimulated the expression of phospho-p38 MAPK in a concentration-dependent manner. SB203580, a specific p38 MAPK inhibitor, blocked such effects.Aspirin exhibits a biphasic effect on the apoptosis in BAEC, reducing apoptosis at low concentration and inducing apoptosis at high concentration. p38 MAPK may be an important signal molecule mediating the effects of aspirin.

p28, a 28kD protein from toad (Bufo bufo gargarizans) oocytes, was identified by using p13 suc1 -agaroseaffinity chromatography. Sequence homology analysis of the full-length cDNA of p28(Gene Bank accessionnumber: AF 314091) indicated that it encodes a protein containing 224 amino-acids with about 55% iden-tities and more than 70% positives to human, rat or mouse UCH-L1, and contains homological functionaldomains of UCH family. Anti-p28 monoclonal antibody, on injecting into the oocytes, could inhibit theprogesterone-induced resumption of meiotic division in a dose-dependent manner. The recombinant pro-tein p28 showed similar SDS/PAGE behaviors to the native one, and promoted ubiquitin ethyl ester hydrolysis,a classical catalytic reaction for ubiquitin carboxyl terminal hydrolases (UCHs). The results in this paperreveal that a novel protein, p28, exists in the toad oocytes, is a UCH L1 homolog, was engaged in the processof progesterone-induced oocyte maturation possibly through an involvement in protein turnover anddegradation.Key words: p28, cDNA clone, recombinant expression, ubiquitin carboxyl terminal hydrolase, oocytematuration.

The hypothesis is that the use of transient receptor potential (TRP) channel agonist could be helpful in promoting bone regeneration and anti-osteoporosis. Key words: Transient receptor potential channel, bone repair, bone regeneration, osteoporosis, pharmacology.

Histamine is released into the systemic circulation during anaphylaxis, by drugs and by surgical procedures. Studies in animal models have conclusively demonstrated that released cardiac histamine is a major mediator of arrhythmias that occur during anaphylaxis and following the administration of histamine-releasing drugs. Several lines of evidence suggest a similar arrhythmogenic role for cardiac histamine in humans: (1) The human heart is rich in histamine; (2) cardiac histamine can be readily released from human heart in vitro by therapeutic concentrations of drugs; (3) histamine has potent arrhythmogenic effects on the human heart in vitro. Arrhythmogenic effects of histamine include enhancement of normal automaticity, induction of abnormal automaticity, induction of triggered tachyarrhythmias, depression of atrioventricular conduction, and increase in the vulnerability of the ventricles to fibrillation. A combination of H1 and H2 antihistamines is needed to block the arrhythmogenic effects of histamine. Certain arrhythmogenic effects of histamine (e.g. induction of slow responses and delayed afterdepolarizations) can also be blocked by drugs which inhibit the influx of cations through slow channels. In contrast, the commonly-used drug digitalis potentiates the arrhythmogenic effects of histamine. We propose that histamine release produced by drugs and surgical procedures may be an overlooked factor in fatal cardiac arrhythmias. Experimental studies suggest that selective pharmacological methods can be developed to block the arrhythmogenic effects of histamine.

We have developed an anatomically and functionally intact preparation of isolated pectinate muscles from readily-available surgical specimens of human right atrial appendage. Individual pectinate muscles (2-3 per specimen) are dissected free and mounted in a tissue bath. Field stimulation is used for electrical pacing, and isometric contractions are recorded. The pectinate muscle develops a stable and large force of contraction and hence is superior to strips cut from atrial appendage specimens. Isolated pectinate muscles develop spontaneous beating or can be induced to beat spontaneously by brief periods of electrical pacing or transient exposure to epinephrine or histamine. Spontaneously-beating muscles increase their rate and force of contraction in response to drugs which have positive chronotropic and inotropic effects in the whole heart. Because the force of contraction of the pectinate muscle is a function of the rate of beating, inotropic effects of agents should also be evaluated in preparations which are electrically paced at a constant rate.

Platelet-activating factor is a novel phospholipid that has been implicated as an important mediator of acute allergic reactions. The intravenous administration of acetyl glyceryl ether phosphorylcholine, a pure, synthetic platelet-activating factor, causes electrocardiographic changes in the rabbit similar to those which are characteristic manifestations of systemic anaphylaxis. To determine whether platelet-activating factor contributes to anaphylactic cardiac dysfunction, we measured platelet-activating factor release from the sensitized guinea pig heart challenged in vitro with specific antigen and compared the resulting cardiac dysfunction with that induced by the injection of acetyl glyceryl ether phosphorylcholine into nonsensitized hearts. The results of these studies document that, during anaphylaxis in the isolated guinea pig heart, a platelet-activating factor is released into the coronary effluent that has physicochemical and functional properties similar to those of acetyl glyceryl ether phosphorylcholine. The intracardiac administration of acetyl glyceryl ether phosphorylcholine (10(-14) to 3 X 10(-9) mol) induced dose-related decreases in left ventricular contractile force (-5 to -85%) and coronary flow (-5 to -85%), as well as impaired atrioventricular conduction. The negative inotropic effect of acetyl glyceryl ether phosphorylcholine also was present in hearts perfused at constant flow. Although, in these hearts, acetyl glyceryl ether phosphorylcholine increased coronary resistance, which may have caused regional shunting and ischemia, it is unlikely that the negative inotropic effect of acetyl glyceryl ether phosphorylcholine was secondary to changes in coronary flow, since acetyl glyceryl ether phosphorylcholine also caused a dose-dependent negative inotropic effect in the electrically paced, noncoronary-perfused left atrium and right ventricular papillary muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Data from our laboratory indicate that the heart reacts as a target organ in systemic hypersensitivity reactions (Capurro and Levi, 1975; Graver et al., 1983). Cardiac dysfunction observed during anaphylaxis in the guinea pig (Capurro and Levi, 1975; Zavecz and Levi, 1977) resembles that reported in humans (Bernreiter, 1959; Both and Patterson, 1970; Criep and Woehler, 1971; Petsas and Kotier, 1973; Sullivan, 1982) and is caused by mediators released intracardially and reaching the heart from the lung (Zavecz and Levi, 1977). “Cardiac anaphylaxis” (Feigen and Prager, 1969) is characterized by tachycardia, arrhythmias, contractile failure, coronary constriction, and mediator release (Capurro and Levi, 1975; Levi and Allan, 1980; Levi et al., 1982). Tachycardia and arrhythmias are caused by the release of endogenous cardiac histamine, since they are reproduced by the intracardiac administration of histamine and abolished by antihistamines (Levi and Allan, 1980; Levi et al., 1982). On the other hand, anaphylactic coronary constriction is markedly reduced by cyclooxygenase inhibitors such as indomethacin or aspirin or by thromboxane syn-thetase inhibitors such as 1-(2-isopropylphenyl)imidazole (Allan and Levi, 1981). Furthermore, the intracardiac administration of U 46619, a stable thromboxane analogue, causes coronary constriction (Allan and Levi, 1980a). Thus, prostanoate compounds, particularly thromboxane, contribute to the fall in coronary flow rate that characterizes cardiac anaphylaxis (Levi et al., 1982). Other potent coronary-constricting agents, such as platelet-activating factor (PAF, AGEPC), are also likely to contribute to anaphylactic coronary constriction (Levi et al., 1984).