A quasi-randomized controlled trial of Ninjin'yoeito for the treatment of postpartum anemia and the prevention of postpartum depression.

AIM: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD). METHODS: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment. RESULTS: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93). CONCLUSION: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD.

Subretinal implantation of Okayama University-type retinal prosthesis (OURePTM) in canine eyes by vitrectomy.

Okayama University-type retinal prosthesis (OURePTM) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. This study aims to test surgical feasibility of subretinal implantation and functional durability of dye-coupled films in the subretinal space. The dye-coupled films were implanted subretinally by 25-gauge vitrectomy in the right eye of 11 normal beagle dogs: 2 dogs served for film removal after 5-month film implantation, 3 dogs for film removal after 3-month film implantation, 3 dogs for 3-month film implantation and pathological examination, and 3 dogs for sham surgery. The surface electric potential of the removed dye-coupled films in response to light was measured by the Kelvin Probe system. At surgery, rolled-up dye-coupled films in 5 × 5 mm square size could be inserted into subretinal space of retinal detachment induced by fluid injection with a 38-gauge polyimide tip. Retinal attachment was maintained by silicone oil injection in vitreous cavity. At autopsy, the retina in all dogs maintained the ganglion cell layer, inner and outer nuclear layers while it lost the outer segments in some part. All 5 sheets of removed dye-coupled films maintained the dye color. One sheet of the 5-month implanted film showed proportional increase of surface potential in response to increasing light intensity. Subretinal implantation of OURePTM by vitrectomy was technically feasible in canine eyes, and OURePTM maintained the function of generating light-evoked surface potential after 5 months in subretinal implantation.

Structure-activity relationship study on alpha1 adrenergic receptor antagonists from beer.

Hordatine A and aperidine have been previously isolated from beer as active ingredients, which bind to muscarinic M3 receptor. In addition, these compounds have exhibited antagonist activity against the alpha1A adrenoceptor. Although the relative structures of these two molecules have previously been determined, the absolute stereochemistry was unclear. Hence, to elucidate the absolute stereochemistry of natural hordatine A, we synthesized each enantiomer of hordatine A and aperidine from optically pure dehydrodi-p-coumaric acid. Several additional related compounds were also synthesized for structure-activity relationship studies. Chiral column HPLC analysis demonstrated that the absolute stereochemistry of natural hordatine A is (2S,3S), while based on the isomerization mechanism, the stereochemistry of aperidine is (2R,3S). The alpha1A adrenoceptor binding activity of (2R,3R)-hordatine A is the most potent among the enantiomeric pairs of hordatines and aperidines. Furthermore, the related, synthetic compound, (2R,3R)-methyl benzofurancarboxylate exhibits antagonist activity against the alpha1A adrenoceptor at a lower concentration than that of hordatine A.

Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology.

The surface epithelial cells of the ovary, which are modified peritoneal cells, form a single, focally pseudostratified layer. The Müllerian ducts differentiate after invagination of the coelomic mesothelium over the gonadal ridges during the 6th week of embryonic life. On the basis of the embryologically putative Müllerian potential of this epithelium, endometriosis can be explained by coelomic metaplasia from the peritoneum, including ovarian surface epithelium. Some pelvic endometriosis specimens have shown that epithelial cells on the ovary or pelvis are serially changed to endometriotic gland cells. Immunohistochemistry as well as scanning electron microscopy also reinforce the light-microscopical findings. A three-dimensional culture system demonstrated that human ovarian surface epithelial cells exhibited a glandular-stromal structure when they were cocultured with endometrial stromal cells in an estrogen-rich environment. Ovarian carcinomas in the epithelial-stromal category are thought to arise from the surface epithelium and its inclusions. The ovarian surface epithelium is physiologically involved in follicular rupture, oocyte release, and the subsequent repair of follicle wall during reproductive age. Simultaneously, ovulation may cause a loss of integrity of the surface epithelium, followed by accumulation of multiple mutations. The cortical invagination, surface stromal proliferation, and Müllerian differentiation of these cells are likely not to be an early step in the cancer development. However, the inclusion cysts are closely related with carcinogenesis because they are significantly more common in ovaries contralateral to those containing epithelial cancers than in control ovaries. As an in vitro study, ovarian carcinoma cell lines were established from simian virus 40 large T antigen-transformed human surface epithelial cells of the ovary. Further investigations of these cell lines may lead to insights into the preneoplastic and early stages of carcinomas. To clarify the pathogenesis of endometriosis and epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium are required.

Synthesis, properties, and NAD+-NADH-type redox ability of 14-substituted 1,3-dimethyl-5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3h)-dionylium tetrafluoroborates and their hydride adducts.

A synthesis of 14-substituted 1,3-dimethyl-5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates 11a,b(+).BF4- was accomplished by the methylation of 5,10-methanocycloundeca[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dione derivatives with MeI and following anion-exchange reaction by treatment with 42% aq HBF(4). Compound 11b(+).BF4- was synthesized alternatively by the reaction of 1,6-methano[11]annulenylium tetrafluoroborate with 6-phenylamino-1,3-dimethyluracil and following oxidative cyclization reaction. Remarkable structural characteristics of 11a,b(+)were clarified on inspection of the UV-vis and NMR spectral data as well as X-ray crystal analyses. The stability of cations 11a,b(+)() is expressed by the pK(R+) values which were determined spectrophotometrically as 9.8 and 9.7, which are smaller by 1.4 and 1.2 pH units than those of the corresponding seven-membered ring cations, respectively; however, the values are larger by 3.6 and 3.5 pH units than that of the parent 1,6-methano[11]annulenylium ion (pK(R+) = 6.2). The feature is rationalized on the basis of the perturbation derived from the bond fixation of the parent cation and the electron-donating ability of pyrrolopyrimidine. The electrochemical reduction of 11a,b(+).BF4- exhibited reduction potential at -0.58 and -0.52 (V vs Ag/AgNO3) upon cyclic voltammetry (CV). Reaction of 11a(+).BF4- with hydride afforded mixures of the C13- and C11-adducts in a ratio with hydride afforded, on the other hand, the C13-adduct as a single product. In both cations, the methano-bridge seemed to control the nucleophilic attack to the C13 favorably with exo-selectivity. The photoinduced autorecycling oxidation reactions of 11a,b(+).BF4- toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 1.1 to 32.2. Furthermore, as an example of the NAD+-NADH models, the reduction of a pyruvate analogue and some carbonyl compounds with the hydride adducts of 11a,b+.BF4- was accomplished for the first time to give the corresponding alcohol derivatives.

Synthesis, properties, and oxidizing ability of areno-annulated 1,3-dimethyl-10-phenylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine- 2,4(1,3H)-dionylium ions.

[structures: see text] Novel areno-annulated 1,3-dimethyl-10-phenylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ions 12a,b+ x BF4(-) and 16a+ x BF4(-) were synthesized by three-step reactions, starting from the reactions of benzo[b]tropone and naphtho[2,3-d]tropone with 6-anilino-1,3-dimethyluracil. Structural characteristics of 12a,b+ and 16a+ were clarified on inspection of the UV-vis and NMR spectral data as well as by X-ray crystal analyses. The stability of cations 12a,b+ and 16a+ is expressed by the pK(R+) values which were determined spectrophotometrically as the values of ca. 0.5-9.0. The pK(R+) value of the naphtho[b]tropylium ion 4+ was clarified to be much lower, at <0. The electrochemical reduction of 12a,b+ and 16a+ exhibited reduction potentials at -0.46 to -0.67 (V vs Ag/AgNO3) upon cyclic voltammetry (CV). The reduction potentials of the benzotropylium ion and cation 4+ were -0.26 and -0.09 V, respectively. In a search for reactivity, reactions of 12a,b+ x BF4(-) with some nucleophiles, hydride and diethylamine, were carried out. Although the reactions of 12a+ x BF4(-) afforded C11 adduct 19 as a single product, the addition reactions of 12b+ x BF4(-) proceeded at both C9 and C11. The attempted reduction of methyl benzoylformate by using 21 was carried out unsuccessfully. The photoinduced oxidation reaction of 12a,b+ x BF4(-) and 16a+ x BF4(-) toward some amines under aerobic conditions was carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling number of 3.6-21.7.

Novel synthesis, properties, and NAD+-NADH type redox ability of 1,3-dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine- 2,4(1,3h)-dionylium ions annulated with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4h)-dione and furan analogue, and their hydride adducts.

[reaction: see text] A convenient preparation of novel cations 11a,b+ x BF4(-) and 12a,b+ x BF4(-), which are derived from annulation of the 1,3-dimethylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dionylium ion with additional pyrrolo[2,3-d]pyrimidine-1,3(2,4H)-dione and a furan analogue, was accomplished by a novel oxidative cyclization of 1,7-dihydro-7-[1',3'-dimethyl-2',4'(1',3'H)-dioxo-6'-(phenylamino)-pyrimidin-5'-yl]-1,3-dimethyl-10-phenylcyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1,3H)-dione 9 and its furan-analogue by using DDQ or photoirradiation under aerobic conditions. Structural characteristics of 11a,b+ and 12a,b+ were clarified on inspection of the UV-vis and NMR spectral data as well as X-ray crystal analyses. The stability of cations 11a,b+ and 12a,b+ is expressed by the pK(R+) values that were determined spectrophotometrically to be 10.7-12.6. The electrochemical reduction of 11a,b+ x BF4(-) and 12a,b+ x BF4(-) exhibited reduction potential at -0.93 to -1.00 (V vs Ag/AgNO3). The first reduction potential of 11a+ was reversible due to steric hindrance of two phenyl groups. The photoinduced oxidation reaction of 11a,b+ x BF4(-) and 12a,b+ x BF4(-) toward some amines under aerobic conditions was carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) with the recycling numbers of 0.6-30.3. Furthermore, as an example of the NAD+-NADH models, the reduction of a pyruvate analogue and some carbonyl compounds with the hydride-adduct of 11a+ x BF4(-) was accomplished for the first time to give the corresponding alcohol derivatives.

Novel synthesis, static and dynamic properties, and structural characteristics of 5-cyano[n](2,4)pyridinophane-6-ones (n= 9-6) and their chemical transformations.

A novel synthesis of 5-cyano[n](2,4)pyridinophane-6-ones 12a-d (n= 9, 8, 7, and 6) consists of allowing cyanoacetatoamide to react with cycloalk-2-enones. Their static and dynamic properties as well as structural characteristics are studied on the basis of their spectroscopic properties, cyclic voltammetry, and theoretical calculations. The (1)H and (13)C NMR spectra at various temperatures have clarified the dynamic behavior of the methylene chains for [7](2,4)- and [6](2,4)pyridinophane-6-one derivatives 12c and 12d. The energy barrier (Delta G(++)) of the bridge flipping of 12c is estimated to be 12.0 kcal mol(-1)(T(c)= 0 degree C). On the other hand, compound 12d undergoes pseudorotation (conformational change of the methylene chain) at room temperature, and does not undergo bridge flipping even at 150 degree C in DMSO-d(6). The energy barrier (Delta G(++)) of the pseudorotation of the methylene chain 12d of is found to be 10.5 kcal mol(-1)(T(c)=-25 degree C), and thus, two stable conformers of the hexamethylene bridge of 12d are determined as predicted by theoretical calculations. Deformation of the pyridone ring of 12d is also determined by X-ray crystallographic analysis. Furthermore, chemical transformations of 12a-c leading to 5-carbamoyl[n](2,4)pyridinophanes 15a-c are also accomplished successfully in moderate to good yields.

New synthesis, properties, and oxidizing ability of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin- 2,4(1,3H)-dionylium tetrafluoroborate.

A novel synthesis of 1,3-dimethyl-5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate (10(+).BF(4)(-)) was accomplished by the reaction of 3,8-methano[11]annulenone with dimethylbarbituric acid and following acidic cyclization, albeit in low yield. Remarkable structural characteristics were suggested on inspection of the spectral data and MO calculation, and it was clarified that the positive charge is largely localized at the C11. The pK(R+) value of cation 10(+) was determined spectrophotometrically to be 4.6, which is much smaller by 4.1 pH unit than that of 1,3-dimethyl-7,12-methanocycloundeca[4,5]furo[2,3-d]pyrimidin-2,4(1,3H)-dionylium tetrafluoroborate (pK(R+) = 8.7). This value is also smaller by 1.6 pH unit than that of the parent 1,6-methano[11]annulenylium ion (pK(R+) = 6.2). The feature is rationalized on the basis of the perturbation derived from the bond fixation of the parent cation. The electrochemical reduction of 10(+) exhibited less negative reduction potential at -0.39 (V vs Ag/AgNO(3)) upon cyclic voltammetry (CV). In a search for reactivity, reactions of 10(+) with some nucleophiles, hydride and diethylamine, were carried out to give mixtures of C11- and C13-adducts. In both reactions, the methano-bridge controls the nucleophilic attacks to the C13 to favor exo selectivity. The photoinduced autorecycling oxidation reactions of 10(+).BF(4)(-) toward some amines under aerobic conditions were carried out to give the corresponding imines (isolated by converting to the corresponding 2,4-dinitrophenylhydrazones) in 719-3286% yield (recycling number of 10(+).BF(4)(-): 7.2-32.9).

Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea, on neutrophil chemotaxis in vitro and in vivo.

The effect of (-)-epigallocatechin 3-gallate (EGCG), a major polyphenol of green tea, on neutrophil migration has been studied using multiwell-type Boyden chambers in vitro and a fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA)-induced rat allergic inflammation model in vivo. EGCG inhibited rat neutrophil chemotaxis toward cytokine-induced neutrophil chemoattractant-1 (CINC-1) in a concentration-dependent manner. In addition, CINC-1-induced neutrophil chemotaxis was suppressed by the pretreatment of rat neutrophils with EGCG at the concentration over 15 microg/mL. EGCG caused concentration-dependent suppression of the transient increase in CINC-1-induced intracellular free calcium level in both rat neutrophils and rat CXC chemokine receptor 2 (CXCR2)-transfected HEK 293 cells. EGCG inhibited CINC-1 production by IL-1beta-stimulated rat fibroblasts (NRK-49F cells) and lipopolysaccharide-stimulated rat macrophages at the concentration over 50 microg/mL, a comparatively high concentration. Oral administration of EGCG (1.0 mg or 1.5 mg/rat) at 1 h before the challenge with FITC-OVA suppressed neutrophil infiltration into the air pouch (inflammatory site) in the air-pouch type FITC-OVA-induced allergic inflammation in rats. Chemokine levels in the pouch fluids, however, were not influenced by EGCG administration. The results suggest that EGCG suppressed neutrophil infiltration by a direct action on neutrophils, but not by indirect actions, including the suppression of chemokine production at the inflammatory site.

Novel synthesis and oxidizing ability of tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones.

Convenient preparation of novel tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones, 12a(+).BF(4)(-) and 12b(+)().BF(4)(-), consists of a reaction of 2-methoxytropone with dimethylbarbituric acid to give 7,9-dimethyl-3-[1',3'-dimethyl-2'(1'H),4'(3'H),6'(5'H)-trioxopyrimidin-5'-ylidene]cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione 8 and the following oxidative cyclization by using DDQ or photoirradiation under aerobic conditions. On the basis of the MO calculations, the selectivity of two types of oxidative cyclization reactions of 8 was rationalized. X-ray crystal analyses and MO calculations were carried out to clarify the structural characteristics of 12a(+). BF(4)(-) and 12b(+).BF(4)(-). The stability of cations 12a(+) and 12b(+) is expressed by the pK(R) + values which were determined spectrophotometrically as 8.8 and 8.6. The electrochemical reduction of 12a(+) and 12b(+) exhibited reduction potential at -0.63 and -0.62 (V vs Ag/AgNO(3)), respectively. Reactions of 12a(+)().BF(4)(-) and 12b(+)().BF(4)(-) with some nucleophiles, hydride and diethylamine, were carried out to clarify that the reactivity of 12a(+)().BF(4)(-) and 12b(+).BF(4)(-) was substantially dependent on the annulating position. The oxidizing ability of 12a(+).BF(4)(-) and 12b(+).BF(4)(-) toward alcohols and amines in the autorecycling process was demonstrated as well.

Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation.

PURPOSE: In this study, we examined the promoter methylation status and expression of 14-3-3 sigma and evaluated its clinical significance in epithelial ovarian cancer. EXPERIMENTAL DESIGN: Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3 sigma gene and protein. RESULTS: Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P < 0.001). Treatment of 5-aza-2'-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3 sigma protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3 sigma protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3 sigma was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of >2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3 sigma immunoreactivity was significantly associated with overall survival (P = 0.0058). CONCLUSIONS: Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.

Novel synthesis and properties of 1,6-methanocycloundeca[b]pyrimido[5,4-d]pyrrole-12,14-dione derivatives: autorecycling oxidation of some amines and alcohols.

Novel 1,6-methanocycloundeca[b]pyrimido[5,4-d]pyrrole-12,14-dione derivatives 6a,b and 7a-c were synthesized in moderate to good yields by the enamine alkylation and dehydrating condensation reactions of 11-chloro-3,8-methano[11]annulenone (8) with 6-amino-3-substituted uracil derivatives and subsequent elimination of HCl. The (1)H NMR spectra clarified that compounds 6a,b and 7a-c are aromatic molecules having a diatropic pi-system, which is suggested by the chemical shifts of the bridge methylene protons and peripheral protons. The electrochemical reduction exhibited more positive reduction potentials as compared with those of the vinylogous compounds of cyclohepta[b]pyrimido[5,4-d]pyrrole derivatives. In a search for the oxidizing function of 6a,b and 7a-c, compounds 6a and 7b were demonstrated to oxidize benzylamines, cyclohexylamine, and benzyl alcohol to give the corresponding carbonyl compounds in more than 100% yield under aerobic and photoirradiation conditions, while only benzylamine was oxidized under aerobic and thermal conditions at 100 degrees C. Thus, compounds 6a and 7b oxidize amines and alcohols in an autorecyling process, and the efficiency is higher under photoirradiation as compared with the thermal process, suggesting the oxidation reaction probably proceeds via electron transfer from amine and alcohol to the excited and ground states of compounds 6a and 7b.

Novel synthesis, properties, and oxidizing ability of 11,13-disubstituted 3,8-methanocycloundeca[8,9-b]pyrimido[5,4-d]-furan-12(11H),14(13H)-dionylium tetrafluoroborates.

Synthesis of novel 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2',4',6',8',10'-pentaenylidene)pyrimidine-2(1H),4(3H),6(5H)-trione] derivatives 10a-c was accomplished. Their structural characteristics were investigated on the basis of the 1H and 13C NMR and UV-vis spectra. Upon treatment with DDQ, 10a-c underwent oxidative cyclization to give novel 11,13-disubstituted 3,8-methanocycloundeca[8,9-b]pyrimido[5,4-d]furan-12(11H),14(13H)-dionylium tetrafluoroborates 11a-c*BF4- in good yields. The spectroscopic properties of 11a-c*BF4- were studied, and the structural characterization of 11b*BF4- was performed by the X-ray crystal analysis. Cations 11a-c were very stable, and their pKR+ values were determined spectrophotometrically to be 8.3-8.9. The electrochemical reduction of 11a-c exhibited low reduction potentials at -0.43 to -0.45 (V vs Ag/AgNO3) upon cyclic voltammetry (CV). In a search for reactivity, reactions of 11a*BF4- with some nucleophiles, hydride and diethylamine, were carried out to clarify that the methano-bridge controls the nucleophilic attacks to occur with endo-selectivity. The photoinduced oxidation reactions of 11a*BF4- toward some amines under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield.

Synthesis, properties, and oxidizing ability of 9,11-dimethylbenzocyclohepta[6,7-b]pyrimido[5,4-d]furan- 10(9H),12(11H)-dionylium tetrafluoroborate.

Convenient preparation of novel 9,11-dimethylbenzocyclohepta[6,7-b]pyrimido[5,4-d]furan-10(9H),12(11H)-dionylium tetrafluoroborate 11*BF4- consisted of a condensation reaction of benzo[d]tropone with dimethylbarbituric acid and following oxidative cyclization reaction by using DDQ-Sc(OTf)3 or photoirradiation under aerobic conditions. Alternative synthesis of 11*BF4- was also accomplished by a condensation reaction of 2-methoxybenzo[d]tropone with dimethylbarbituric acid and a subsequent cyclization reaction by using 42% aq HBF4. The X-ray crystal analysis and MO calculation were carried out to clarify the structural characteristics. Properties of the cation 11 were studied by the pKR+ value (4.7) and reduction potentials (-0.46 and -1.07 V vs Ag/AgNO3) as well as the reaction with some nucleophiles. The oxidizing ability of 11*BF4- toward alcohols in the autorecycling process was demonstrated as well.

Roles of luteinizing hormone/chorionic gonadotropin receptor in anchorage-dependent and -independent growth in human ovarian surface epithelial cell lines.

Epithelial ovarian carcinomas are thought to arise from cells of ovarian surface epithelium (OSE) covering the free surface of the human ovary. Two immortalized human cell lines, OSE2a (non-tumorigenic) and OSE2b-2 (tumorigenic), were previously established from normal OSE cells of a reproductive-age patient. In the present study, we found that expression of luteinizing hormone (LH)/chorionic gonadotropin (CG) receptor (LH/CGR) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10(3) mIU/ml) of CG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10(5) mIU/ml) of CG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/CGR-related tumorigenicity, we compared cDNA expression arrays of OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin beta 1, intercellular adhesion molecule-1 (ICAM1), and Waf1/Cip1. Subsequent semiquantitative reverse transcription polymerase chain reaction using OSE2a cells showed that expression of integrin beta 1 was down-regulated by a high concentration (10(5) mIU/ml) of CG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin beta 1. Repetitive and excessive activation of LH/CGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression.

Synthesis, stability, and spectroscopic and electronic properties of three benzocyclohepta[alpha]azulenylium ions.

Novel pi-systems, three benzocyclohepta[alpha]azulenylium ions, 7a-c, are synthesized, and their stability and properties have been characterized in terms of the position of the benzo-annulation and compared with those of the parent cyclohepta[alpha]azulenylium ion 4. Benzocyclohepta[6,7-alpha]azulenylium ion (7a) (p K R+ = 7.3, E red = -0.567 V vs Ag/Ag+) and benzocyclohepta[6,5-alpha]azulenylium ion (7b) (p K R+ = 5.1, E red = -0.482 V vs Ag/Ag+), which are annulated with benzene on the position having a high bond order of 4, are not appreciably destabilized compared with cyclohepta[alpha]azulenylium ion (4) (p K R+ = 7.3, E red = -0.458 V vs Ag/Ag+). On the other hand, benzocyclohepta[7,6-alpha]azulenylium ion (7c) (p K R+ = 1.6, Ered = -0.197 V vs Ag/Ag+) is considerably destabilized, probably due to enhanced contribution of the quinoid structure of the benzene ring, which is annulated on the position having a low bond order of the cyclohepta[alpha]azulenylium ion moiety. Furthermore, the cations 7a and 7b are more stable than 12,13-dihydrobenzocyclohepta[7,6-alpha]azulenylium ion (25) (p K R+ = 4.8, E red = -0.513 V vs Ag/Ag+), which is a dihydrogenated compound of 7a, while 7c is less stable than 25. These features are reflected in the considerable red shift of the longest absorption maximum of the electronic spectrum of 7c, as compared with those of 4, 7a, and 7b, and in the chemical shifts of the protons and their coupling constants of the (1)H NMR spectra. Furthermore, the (1)H NMR spectra and electronic spectra of 5H-benzocyclohepta[6,7-alpha]azulen-5-one (8a) and 7H-benzocyclohepta[6,5-alpha]azulen-7-one (8b) in acidic media have also been studied to clarify the spectral characteristics similar to those of 7a and 7b.