Radical one-pot α,ß-dual and ß-mono-oxymethylation of alkylidenemalonate.

Dimethylzinc-mediated radical conjugate addition reaction of dimethyl alkylidenemalonates with iodomethyl pivalate gave a high yield of the α,ß-dual oxymethylation product in one pot under air and the ß-pivaloyloxymethylation product under argon.

High performance of N-alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition.

Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl-imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.

Effect of melatonin treatment on the developmental potential of parthenogenetic and somatic cell nuclear-transferred porcine oocytes in vitro.

Melatonin secreted from the mammalian pineal gland is a free-radical scavenger that protects tissues from cell damage. The present study examined the effects of addition of melatonin to the culture medium on the developmental potential of parthenogenetic and somatic cell nuclear-transferred (SCNT) porcine oocytes. Supplementation of the maturation medium with melatonin did not increase the maturation rate, the proportion of oocytes that cleaved and developed into blastocysts after parthenogenetic activation, or the blastocyst cell number compared to controls. When 10-7 M melatonin was added to the culture medium, the proportion of parthenogenetic oocytes that developed to the 2-cell and 4-cell stages was significantly higher than that of controls. The potential of melatonin-treated oocytes to develop into blastocysts was high but not significantly different from that of controls. The addition of 10-7 M melatonin to the culture medium did not increase the preimplantation development of SCNT oocytes. Melatonin treatment significantly reduced the levels of reactive oxygen species in 4-cell parthenogenetic and SCNT embryos, but did not reduce the proportion of apoptotic cells in parthenogenetic and SCNT blastocysts. Although the results indicated that parthenogenetic and SCNT melatonin -treated embryos had significantly lower levels of reactive oxygen species than controls, the potential of melatonin-treated embryos to develop into blastocysts was not significantly higher than that of controls, in contrast to previous reports. The beneficial effects of melatonin on the developmental potential of oocytes might depend on the culture conditions.

Stereoselective radical addition of an acetal to sterically tuned enantiomerically pure N-sulfinyl imines.

Enantiomerically enriched sulfonamides were synthesized by the radical addition of an acetal to enantiomerically pure N-sulfinyl imines using dimethylzinc-air and boron trifluoride diethyl etherate. Higher levels of stereocontrol were observed by using a mesitylenesulfinyl group. Furthermore, an amine and an amino alcohol with high enantiomeric purity were obtainable from the sulfonamide product.

Case of autoimmune progesterone dermatitis presenting as fixed drug eruption.

Autoimmune progesterone dermatitis is a rare disorder that presents as a cyclical cutaneous eruption during the luteal phase of the menstrual cycle. It typically occurs in women due to an autoimmune phenomenon to endogenous progesterone production. We describe a 34-year-old woman with an erythematous round plaque with blistering, which recurred a few days before her menstrual cycle, at the identical site on the left arm. The diagnosis of autoimmune progesterone dermatitis is made with i.d. skin testing on the affected lesion with progesterone. After the beginning of oral prednisolone (40 mg daily) therapy during menstruation, although slight recurrence appeared, the severity was significantly improved.

Characterization of a functional ZBP-89 binding site that mediates Gata1 gene expression during hematopoietic development.

GATA-1 is a lineage-restricted transcription factor that plays essential roles in hematopoietic development. The Gata1 gene hematopoietic enhancer allowed Gata1 reporter expression in erythroid cells and megakaryocytes of transgenic mice. The Gata1 hematopoietic enhancer activity is strictly dependent on a GATA site located in the 5' region of the enhancer. However, the importance of the GC-rich region adjacent to the 3'-end of this GATA site has been also suggested. In this study, we show that this GC-rich region contains five contiguous deoxyguanosine residues (G(5) string) that are bound by multiple nuclear proteins. Interestingly, deletion of one deoxyguanosine residue from the G(5) string (G(4) mutant) specifically eliminates binding to ZBP-89, a Krüppel-like transcription factor, but not to Sp3 and other binding factors. We demonstrate that GATA-1 and ZBP-89 occupy chromatin regions of the Gata1 enhancer and physically associate in vitro through zinc finger domains. Gel mobility shift assays and DNA affinity precipitation assays suggest that binding of ZBP-89 to this region is reduced in the absence of GATA-1 binding to the G1HE. Luciferase reporter assays demonstrate that ZBP-89 activates the Gata1 enhancer depending on the G(5) string sequence. Finally, transgenic mouse studies reveal that the G(4) mutation significantly reduced the reporter activity of the Gata1 hematopoietic regulatory domain encompassing an 8.5-kbp region of the Gata1 gene. These data provide compelling evidence that the G(5) string is necessary for Gata1 gene expression in vivo and ZBP-89 is the functional trans-acting factor for this cis-acting region.

Chemoselective conjugate addition of dimethylzinc-mediated ether and acetal radicals to alkylidenemalonates and asymmetric reactions.

Cyclic and acyclic ether or acetal radicals were generated directly from ethers or acetals by the action of dimethylzinc-air, and their subsequent conjugate addition reaction with alkylidenemalonates afforded the corresponding conjugate adducts in reasonably high yields. The reaction with benzylidenemalonates bearing formyl and imino groups gave chemoselectively the conjugate addition products. The asymmetric reaction of bis(8-phenylmenthyl) benzylidenemalonate proceeded diastereoselectively to provide the adduct with 93:7 dr.

Tin-free radical addition of acyloxymethyl to imines.

Acyloxymethyl radicals were generated from the corresponding iodomethyl esters and successfully underwent addition to the CN bond of N-Ts, N-PMP, and N-Dpp imines by the action of dimethylzinc or triethylborane. Ethyl acetate, toluene, and benzene as well as dichloromethane were suitable solvents. The utility of acyloxymethyl radicals as a hydroxymethyl anion equivalent was highlighted by the facile hydrolysis of the acyloxy moiety of the adducts to give the corresponding amino alcohol derivatives in good to high yield.

Propofol alone and combined with dexamethasone for the prevention of postoperative nausea and vomiting in adult Japanese patients having third molars extracted.

We did a prospective, randomised, double-blind study to evaluate the efficacy and safety of a small dose of propofol alone, and propofol combined with dexamethasone, for the prevention of postoperative nausea and vomiting in adult Japanese patients listed for third molars extractions. One hundred and twenty patients, 55 men and 65 women aged 17-48 years, were given placebo, propofol 0.5mg/kg, or propofol 0.5mg/kg plus dexamethasone 8 mg intravenously at the end of the operation. A standard general anaesthestic was used, including sevoflurane and nitrous oxide in oxygen. Patients' characteristics were comparable in all three groups. The numbers of patients who developed postoperative nausea and vomiting during the 24h after anaesthesia were 8 with propofol (p=0.04), 2 with propofol plus dexamethasone (p=0.001), and 16 with placebo. The antiemetic efficacy of propofol combined with dexamethasone was superior to that of propofol alone (p=0.04). There were no clinically important adverse events. We conclude that a small dose (0.5mg/kg) of propofol combined with dexamethasone 8 mg was more effective than propofol alone for the prevention of postoperative nausea and vomiting in adult Japanese patients having general anaesthesia for extractions of third molars.

Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells.

Transcription factor GATA-1 is essential for erythroid cell differentiation. GATA-binding motifs have been found in the regulatory regions of various erythroid-specific genes, suggesting that GATA-1 contributes to gene regulation during the entire process of erythropoiesis. A GATA-1 germ-line mutation results in embryonic lethality due to defective primitive erythropoiesis and GATA-1-null embryonic stem cells fails to differentiate beyond the proerythroblast stage. Therefore, the precise roles of GATA-1 in the later stages of erythropoiesis could not be clarified. Under the control of a GATA-1 gene hematopoietic regulatory domain, a GATA-1 mutant lacking the N-finger domain (DeltaNF mutant) was over-expressed in mice. These mice exhibited abnormal morphology in peripheral red blood cells (RBCs), reticulocytosis, splenomegaly, and erythroid hyperplasia, indicating compensated hemolysis. These mice were extremely sensitive to phenylhydrazine (PHZ), an agent that induces hemolysis, and their RBCs were osmotically fragile. Importantly, the hemolytic response to PHZ was partially restored by the simultaneous expression of wild-type GATA-1 with the DeltaNF mutant, supporting our contention that DeltaNF protein competitively inhibits the function of endogenous GATA-1. These data provide the first in vivo evidence that the NF domain contributes to the gene regulation that is critical for differentiation and survival of mature RBCs in postnatal erythropoiesis.

Small dose of propofol for preventing nausea and vomiting after third molar extraction.

PURPOSE: The study goal was to evaluate the efficacy and safety of a small dose of propofol for the prevention of nausea and vomiting following third molar extraction. PATIENTS AND METHODS: In a prospective, randomized, double-blinded, placebo-controlled trial, 90 women received placebo or propofol at 2 different doses (0.25 mg/kg, 0.5 mg/kg) (n = 30 of each) intravenously at the end of surgery. A standard general anesthetic technique, including sevoflurane and nitrous oxide in oxygen, was employed throughout the surgical procedure. Emetic episodes and safety assessments were performed during 0 to 3 hours and 3 to 24 hours after after anesthesia. RESULTS: The rate of patients experiencing emesis-free (no nausea, retching, or vomiting) during 0 to 3 hours after anesthesia was 60% with placebo, 66% with propofol 0.25 mg/kg (P =.395), and 90% with propofol 0.5 mg/kg (P =.001); the corresponding rate during 3 to 24 hours after anesthesia was 60%, 63% (P = 0.5), and 87% (P =.02) (P values compared with placebo). No clinically serious adverse effects due to the study drug were observed in any group. CONCLUSIONS: Prophylactic therapy with a small dose (0.5 mg/kg) of propofol is effective for preventing postoperative nausea and vomiting in female patients undergoing general anesthesia for third molar extractions.