Studies using the estrogen receptor alpha knockout uterus demonstrate that implantation but not decidualization-associated signaling is estrogen dependent.
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Ovarian hormonal signaling is essential for proper functioning of the uterus in the establishment of pregnancy. Previous studies have demonstrated that decidualization, a stromal transformation that occurs in response to embryo implantation, can be elicited in the uterus of estrogen receptor alpha knockout (alphaERKO) mice in the absence of the estrogen dependence normally seen in wild-type (WT) mice for this response. While the alphaERKO stromal compartment demonstrated the necessary decidual response, embryo implantation is a process initiated in the epithelial layer, a uterine component that lacks estrogen responsiveness in the alphaERKO. To determine if the alphaERKO uterus would be competent for implantation, donor embryos were transferred into the uterine lumen of WT and alphaERKO females that had been ovariectomized and treated with exogenous estradiol and progesterone to mimic early pregnancy. No implantation occurred in the alphaERKO, while implantation sites containing live embryos were seen in similarly treated WT uteri, indicating that functional estrogen receptor alpha (ERalpha) is required for implantation. Previous observations of estrogen-independent decidualization in the alphaERKO prompted investigation of the mechanism leading to estrogen independence of this process. The disruption of progesterone receptor (PR), Hoxa10, Cox2, or LIF in transgenic mice results in the loss of decidualization response. Therefore, the expression of these genes was studied in WT and alphaERKO uteri by comparing expression following vehicle, progesterone alone (P), or estradiol priming followed by progesterone with nidatory estradiol (E+Pe) and by comparing expression following the above hormonal manipulations in addition to luminal infusion of oil used previously as decidualization-initiating stimulus. The whole-uterus level of PR and Hoxa10 mRNAs did not vary; however, the PR protein was induced in the stroma 24 h after oil infusion. Interestingly, in the WT, this induction was most apparent in samples receiving E+Pe, while in the alphaERKO samples, the induction occurred independent of any hormone priming. Cox2 protein and mRNA increased in both WT and alphaERKO samples 2 h after oil infusion in all three of the treatment groups. In the WT samples, Cox2 levels remained elevated 24 h after oil infusion only in the E+Pe treatment group; however, the elevated Cox2 was seen in samples taken 24 h after oil infusion in all three alphaERKO treatment groups. The alphaERKO uterine tissue appeared to sustain more extensive damage when examined 24 h after oil infusion. Severe trauma, such as crushing of the uterine tissue, has previously been shown to remove the requirement for nidatory estradiol for deciduomas to develop, indicating that the greater susceptibility of alphaERKO uterine tissue to damage from intraluminal oil infusion is contributing to decidualization in the absence of ERalpha. Leukemia inhibitory factor (LIF) mRNA was also induced following estradiol treatment in the WT, but also following oil infusion in WT samples that were not treated with estradiol. In contrast, estradiol does not induce LIF mRNA in the alphaERKO, but oil infusion leads to a robust increase in LIF in all alphaERKO sample groups. LIF binds and activates its membrane receptor, which initiates responses including the phosphorylation and nuclear translocation of Stat3 transcription factor. Thus, Stat3 phosphorylation was studied in WT and alphaERKO samples and found to be induced following oil infusion in all samples. Together, these and previous observations illustrate that estrogen is essential for epithelial proliferation and embryo implantation and that estrogen is dispensable for stromal decidualization in the alphaERKO, as the essential genes and signals required for the response are still induced. (+info)
Gene family of oleosin isoforms and their structural stabilization in sesame seed oil bodies.
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Oleosins are structural proteins sheltering the oil bodies of plant seeds. Two isoform classes termed H- and L-oleosin are present in diverse angiosperms. Two H-oleosins and one L-oleosin were identified in sesame oil bodies from the protein sequences deduced from their corresponding cDNA clones. Sequence analysis showed that the main difference between the H- and L-isoforms is an insertion of 18 residues in the C-terminal domain of H-oleosins. H-oleosin, presumably derived from L-oleosin, was duplicated independently in several species. All known oleosins can be classified as one of these two isoforms. Single copy or a low copy number was detected by Southern hybridization for each of the three oleosin genes in the sesame genome. Northern hybridization showed that the three oleosin genes were transcribed in maturing seeds where oil bodies are being assembled. Artificial oil bodies were reconstituted with triacylglycerol, phospholipid, and sesame oleosin isoforms. The results indicated that reconstituted oil bodies could be stabilized by both isoforms, but L-oleosin gave slightly more structural stability than H-oleosin. (+info)
Increased production of antioxidative sesaminol glucosides from sesame oil cake through fermentation by Bacillus circulans strain YUS-2.
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Bacillus circulans strain YUS-2 was isolated as the strongest antioxidant-producer in fermentation of sesame oil cake (SOC, defatted residue yielded from sesame seed oil production). Two major strong antioxidants from fermented SOC were purified and identified as known sesaminol triglucoside and sesaminol diglucoside, however, our results demonstrated that the fermentation process with B. circulans YUS-2 was highly effective to gain the extraction efficiency of the sesaminol glucosides. (+info)
Antinociceptive effect of a novel long-acting nalbuphine preparation.
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BACKGROUND: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel nalbuphine preparation and to determine its duration of action. METHODS: The antinociceptive effects of i.m. nalbuphine HCl in saline and nalbuphine base in sesame oil were evaluated in rats. The in vitro drug-releasing profiles of nalbuphine HCl and base in different preparations were also evaluated. RESULTS: We found that i.m. nalbuphine HCl 25, 50 and 100 micromol kg(-1) produced dose-related antinociceptive effects with a duration of action of 1.5, 2 and 3 h, respectively. i.m. nalbuphine base 100, 200 and 400 micromol kg(-1) also produced dose-related antinociceptive effects but with longer durations of action: 27, 49 and 55 h, respectively. In vitro studies demonstrated that nalbuphine base in sesame oil had the slowest drug-releasing profile of the different preparations. CONCLUSIONS: i.m. injection of an oil formulation of nalbuphine base produced a long-lasting antinociceptive effect. (+info)
Acute eosinophilic pneumonia associated with intramuscular administration of progesterone as luteal phase support after IVF: case report.
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We report two cases of acute eosinophilic pneumonia induced by i.m. administration of progesterone used as luteal phase support after IVF. For both patients, the symptoms began 3 weeks after the first injection of progesterone. Both patients were in respiratory distress, and one of them required ventilatory assistance for a week, with 5 days in the intensive care unit. Symptoms improved as the i.m. form was shifted to a vaginal form of progesterone together with the administration of corticosteroids. Sesame oil (used as excipient) and benzyl alcohol (used as preservative) could both be incriminated in the development of the hypersensitivity reaction. The need for luteal phase support is clearly established in IVF cycles with GnRH agonist protocols, and progesterone is the generally recommended compound. However, there is no definitive consensus regarding the optimal route of administration of progesterone. These two cases of acute drug-induced disease show that the use of i.m. progesterone can be associated with a severe morbidity in otherwise healthy young patients. This is an additional argument to advocate the use of vaginal progesterone as luteal support in IVF. (+info)
In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.
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A diester prodrug of nalbuphine, sebacoyl dinalbuphine (SDN), and its long-acting formulation are currently being developed to prolong the duration of nalbuphine. A comparative in vitro hydrolysis study was conducted for SDN in rat, rabbit, dog, and human blood. Both SDN and nalbuphine in blood or plasma were measured by high-performance liquid chromatography. The hydrolysis rates of SDN in blood were ranked as follows: rat > rabbit > human > dog. The rapid formation of nalbuphine in the blood accounted for almost 100% of the prodrug, which supported the contention that nalbuphine is the major metabolite after SDN hydrolysis. The hydrolysis profiles of SDN were similar both in plasma and in red blood cells when compared in the blood. In vitro release results of SDN long-acting formulation showed that the rate-limited step of SDN hydrolysis to nalbuphine in blood is the penetration of SDN from oil into the blood. After intravenous administration of SDN in sesame oil into rats, nalbuphine quickly appeared in plasma and, thereafter, exhibited monoexponential decay. Pharmaceutical dosage forms affecting the drug disposition kinetics were demonstrated after intravenous administration. The AUC of nalbuphine was significantly higher and clearance was significantly lower, without changes in the t(1/2) of nalbuphine after intravenous dosing of SDN in sesame oil when compared with that of intravenous dosing with nalbuphine HCl in rats. Overall, these results suggest that SDN fulfilled the original pro-soft drug design in which the prodrug can rapidly metabolize to nalbuphine, and no other unexpected compounds were apparent in the blood. (+info)
Impairment of decidualization in SRC-deficient mice.
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Many signaling events induced by ovarian steroid hormones, cytokines, and growth factors are involved in the process of decidualization of human and rodent endometrium. We have reported previously that tyrosine kinase activation of SRC functionally participates in decidualization of human endometrial stromal cells. To address its essential role in decidualization, we examined, using wild-type and Src knockout mice, whether the process of decidualization was impaired in the absence of SRC. Immunohistochemistry using an antibody specific for the active form of SRC revealed that the active SRC was expressed prominently in the decidualizing stromal cells of the pregnant wild-type mouse. Moreover, the active SRC was upregulated in the uterine horn with artificially stimulated decidual reaction. In comparison with wild-type and Src heterozygous mice, the uterus of Src null mice showed no apparent decidual response following artificial stimulation. Ovarian steroid-induced decidualization in vitro, as determined by morphological changes and expression of decidual/trophoblast prolactin-related protein and prostaglandin-endoperoxide synthase 2 (also known as Cox2), both of which are decidualization markers, did not occur in a timely fashion in endometrial stromal cells isolated from the uteri of SRC-deficient mice compared to those from wild-type and Src heterozygous mice. Our results collectively suggest that SRC is an indispensable signaling component for maximal decidualization in mice. (+info)
Quantitative NMR analysis of a sesamin catechol metabolite in human urine.
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Sesamin, the major sesame oil lignan, is recognized for its health-promoting effects, including the lowering of cholesterol and elevation of gamma-tocopherol in rats and humans. However, little is known about the absorption and metabolism of sesamin in humans. In this study, 6 healthy volunteers took a single dose of sesame oil (508 micromol sesamin) and their urine was collected for four 12-h periods. The urine samples were treated with beta-glucuronidase/sulphatase and extracted with chloroform. The major urinary sesamin metabolite in the chloroform extract was collected using HPLC diode array detector and characterized as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyc lo-[3,3,0]octane using NMR and mass spectroscopy. A quantitative (1)H-NMR technique, based on the methylenedioxyphenyl protons signal (delta 5.91), was used for the quantification of the metabolite in the chloroform extracts of urine. The excretion of the sesamin catechol metabolite ranged from 22.2 to 38.6% (mean +/- SD, 29.3 +/- 5.6) of the ingested dose and happened mainly in the 1st 12 h after ingestion. (+info)