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Fluoxetine's effect on food craving during the luteal phase in women with premenstrual dysphoric disorder (PMDD)
THURSDAY,
SEPTEMBER
7
P4.17.05 FLUOXETINE’S EFFECT ON FOOD CRAVING DURING THE LUTEAL PHASE IN WOMEN WITH PREMENSTRUAL DYSPHORIC DISORDER (PMDD) M. Steiner (l), R. Judge (2), E. Brown (3), and .I. Dillon (2) (1) McMaster university, St. Joseph’s Hospital, Hamilton, Ontario, Canada (2) Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA (3) Eli Lilly and Company, Nederland, CO, USA Objective: A previously reported, placebo-controlled, multi-site trial found fluoxetine effective in mediating PMDD mood symptoms; these data are now used to determine fluoxetine’s effectiveness on eating habits during the luteal phase in women with PMDD. Though cyclical mood, disturbance is the pathognomonic feature of PMDD, a marked change in appetite, overeating or specific food craving is one of the 11 DSM-IV diagnostic criteria for PMDD. Study Methods: Eating habits were assessed in 320 PMDD patients who were randomized to fluoxetine 20mg/day, fluoxetine 60mg/day, or placebo. Symptoms were measured by 2 questions on the self-rated and 1 question on the observer-rated Premenstrual Tension Syndrome Scale (PMTS-SR, PMTS-0). Both scales assessed increase in food intake and specific food cravings. Outcome measure for each woman was her frequency of increased food intake/craving during the luteal phase of the 6 months of treatment. Results: Fluoxetine..treatment (20 and 60 mgiday) statistically significantly reduced the frequency of increased food intake/craving compared with placebo treatment when measured on the PMTS-SR (p
P4.17.06 FUNCTION OF ARG-GLY-ASP (RGD)-BINDING SITES ON fll INTEGRIN IN HUMAN DECIDUAL CELLS H. Hanashi (l), S. Shiokawa (l), K. Sakai (l), N. Suzuki (1)) K. Noguchi (l), M. Higashi (l), M. Hashimoto (l), M. Iwashita (l), Y. Nakamura (l), Y. Kasuga (2) (1) Dept. OBIGYN, Kyorin University School of Medicine, Tokyo, Japan (2) Dept. OBIGYN, Ashikaga Red Cross Hospital, Tochigi, Japan Objectives: Amino acid residues 140-164 of integrin fll comprise on Arg-Gly-Asp (RGD) cross-linking region. The present study was undertaken to study the role of the RGD cross-linking region of integrin fll submit in embryo implantation. Study Methods: A synthetic peptide used in this study was derived from the long arm of the integrin fll chain, residue numbers 140-164 (DDL, DYPIDLYYLMDLSYSMKDDLENVKS). A variant peptide (AAL, DYPIDLYYLMDLSYSMKAALENVKS), in which both Asp 157 and Asp 158 were replaced by Ala, was also used. Embryo attachment and spreading assays were performed using cultured human decidual cells. Mouse blastocysts obtained at 96h after hCG injection were cultured on decidual cells. Decidual cells were cultured without or with synthetic peptides, at concentrations of 1 to 100nM. Measurements of embryo hatching and attachment were made at 12h and 24h of incubation. The area of embryo outgrowth was measured using a color image analyzing system (~~500) between 48h and 96h of incubation. Results: Treatment of decidual cells with synthetic peptides did not affect the rates of hatching and attachment of blastocysts. The outgrowth of embryos on decidual cells was inhibited by DDL peptide in a dosedependent manner, but not by AAL peptide. Conclusions: The present data demonstrated that integrin fll [140-1641 in decidual cells may be important in embryonic development and differentiation following attachment.
147
P4.17.07 HISTOMORPHOMETRIC OVARIAN ASPECTS OF ADULT PINEALECTOMIZED RATS. JM EC Baracat, CE Lang; MA Haidar, MJ SimBes, EL Dair, G Rodrigues de Lima. Department of Gynecology Escola Paul&a de Medicina, Federal University of SBo Paula, Brazil. Objective: The aim of this work was to evaluate the histomorphology of interstitial cells of ovarian stroma in pinealectomized rats. Study Methods: Twenty-six rats were divided in three groups after three normal cycles: GI Control group (n=9); GII Sham pinealectomized rats (n=6); GIII Pinealectomized rats (n=ll). After two months, all animals in estrous phase were sacrificed and the ovary was removed and fixed in 10% formaldehyde. The material was processed by H.E. and Masson Trichrome. Besides analyzing of the morphology of the ovarian stroma, we calculated the maximum diameter of the interstitial cell nuclei. Results: The pinealectomized animals presented larger concentration of interstitial cells in the ovarian stroma. The histomorphometrical analyses revealed that the maximum diameter of the nuclei of the interstitial cells was much larger in pinealectomized rats than in the other groups. Conclusion: Our data suggest that larger metabolic activity and possibly larger hormonal production too could be taking place in these cells.
P4.17.08 IDENTIFICATION AND CHARACTERIZATION OF HUMAN 2OaHYDROXYSTEROID DEHYDROGENASE T. Nakaiima (l), M. Nishizawa (2), K Yasuda (l), S. Ito (2), H. Kanzaki (1) Dept OBIGYN, Kansai Medical University, Osaka, Japan (2) Dept Medical Chemistry, Kansai Medical University, Osaka, Japan Objective: 20a-hydroxysteroid dehydrogenase (HSD) belongs to aldoketo reductase (AKR) superfamily and catalyzes the reaction of progesterone to 20a-Hydroxyprogesterone, which is biological inactive form. Rat 20&-HSD gene was cloned and analyzed by human 20&-HSD was not. The aim of this study was to investigate human 20&-HSD to understand progesterone metabolism. Study Methods: genomic library by hybridization with rat 20&-HSD [AKRlC8] cDNA and performed high-stringency polymerase chain reaction (PCR) for hybridization positive clones with gene-specific primers. Four genes were isolated. We examined the expression of these genes by reverse transcription PCR in various human tissues and the substrate specificity using recombinant enzymes. Results: We isolated four aldo-keto reductase genes which shared high homology; human 20&-HSD [AKRlCl], bile acid-binding protein (BABP) {AKRlC2], prostaglandin F synthase (PGFS)[AKRlCS], and dihydrodiol dehydrogenase (DD) 4 [AKRlC4] genes. Human 20&HSD, BABP, and PGFS mRNAs were expressed ubiquitously, while DD4 mRNA was restricted in the liver. The four recombinant enzymes showed distinct substrate specificity. Conclusion: Human gene coding for the progesterone-metabolizing enzymes 20&-HSD was cloned. BABP, PGFS, and DD4 genes, which were highly homologous to 20&-HSD gene, were also cloned. The expression and the substrate specificity of these genes were elucidated.
P4.17.09 IMMUNOMORPHOLOGIC INVESTIGATION OF PUNCTURE BIOPSY SPECIMENS FROM WOMEN WITH PREVIOUS GESTOSIS L.E. J.G. Moisuk, I.M. Ilinsky, I.V. Sergeyko, F Baranova. Research Centre for Obstetrics, Gynecology & Perinatology, Moscow, Russia Objective: Gestosis is known to be a serious pregnancy complication with negative influence on maternal and perinatal outcomes. Also, chronic renal impairment is known as one of the causes of gestosis. We attempted to study immunomorphologic renal changes in women with previous gestosis. Metods: 20 women (mean age 32,0 + 0,4 years) who had had completed pregnancies ( 25% had one and 75% had two or more pregnancies) complicated by severe gestosis underwent renal biopsy performed 8 days 1,5 years later pregnancy completion. Immunomorphologic investigation of these specimens was done.
SEPTEMBER
7
P4.17.05 FLUOXETINE’S EFFECT ON FOOD CRAVING DURING THE LUTEAL PHASE IN WOMEN WITH PREMENSTRUAL DYSPHORIC DISORDER (PMDD) M. Steiner (l), R. Judge (2), E. Brown (3), and .I. Dillon (2) (1) McMaster university, St. Joseph’s Hospital, Hamilton, Ontario, Canada (2) Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA (3) Eli Lilly and Company, Nederland, CO, USA Objective: A previously reported, placebo-controlled, multi-site trial found fluoxetine effective in mediating PMDD mood symptoms; these data are now used to determine fluoxetine’s effectiveness on eating habits during the luteal phase in women with PMDD. Though cyclical mood, disturbance is the pathognomonic feature of PMDD, a marked change in appetite, overeating or specific food craving is one of the 11 DSM-IV diagnostic criteria for PMDD. Study Methods: Eating habits were assessed in 320 PMDD patients who were randomized to fluoxetine 20mg/day, fluoxetine 60mg/day, or placebo. Symptoms were measured by 2 questions on the self-rated and 1 question on the observer-rated Premenstrual Tension Syndrome Scale (PMTS-SR, PMTS-0). Both scales assessed increase in food intake and specific food cravings. Outcome measure for each woman was her frequency of increased food intake/craving during the luteal phase of the 6 months of treatment. Results: Fluoxetine..treatment (20 and 60 mgiday) statistically significantly reduced the frequency of increased food intake/craving compared with placebo treatment when measured on the PMTS-SR (p
P4.17.06 FUNCTION OF ARG-GLY-ASP (RGD)-BINDING SITES ON fll INTEGRIN IN HUMAN DECIDUAL CELLS H. Hanashi (l), S. Shiokawa (l), K. Sakai (l), N. Suzuki (1)) K. Noguchi (l), M. Higashi (l), M. Hashimoto (l), M. Iwashita (l), Y. Nakamura (l), Y. Kasuga (2) (1) Dept. OBIGYN, Kyorin University School of Medicine, Tokyo, Japan (2) Dept. OBIGYN, Ashikaga Red Cross Hospital, Tochigi, Japan Objectives: Amino acid residues 140-164 of integrin fll comprise on Arg-Gly-Asp (RGD) cross-linking region. The present study was undertaken to study the role of the RGD cross-linking region of integrin fll submit in embryo implantation. Study Methods: A synthetic peptide used in this study was derived from the long arm of the integrin fll chain, residue numbers 140-164 (DDL, DYPIDLYYLMDLSYSMKDDLENVKS). A variant peptide (AAL, DYPIDLYYLMDLSYSMKAALENVKS), in which both Asp 157 and Asp 158 were replaced by Ala, was also used. Embryo attachment and spreading assays were performed using cultured human decidual cells. Mouse blastocysts obtained at 96h after hCG injection were cultured on decidual cells. Decidual cells were cultured without or with synthetic peptides, at concentrations of 1 to 100nM. Measurements of embryo hatching and attachment were made at 12h and 24h of incubation. The area of embryo outgrowth was measured using a color image analyzing system (~~500) between 48h and 96h of incubation. Results: Treatment of decidual cells with synthetic peptides did not affect the rates of hatching and attachment of blastocysts. The outgrowth of embryos on decidual cells was inhibited by DDL peptide in a dosedependent manner, but not by AAL peptide. Conclusions: The present data demonstrated that integrin fll [140-1641 in decidual cells may be important in embryonic development and differentiation following attachment.
147
P4.17.07 HISTOMORPHOMETRIC OVARIAN ASPECTS OF ADULT PINEALECTOMIZED RATS. JM EC Baracat, CE Lang; MA Haidar, MJ SimBes, EL Dair, G Rodrigues de Lima. Department of Gynecology Escola Paul&a de Medicina, Federal University of SBo Paula, Brazil. Objective: The aim of this work was to evaluate the histomorphology of interstitial cells of ovarian stroma in pinealectomized rats. Study Methods: Twenty-six rats were divided in three groups after three normal cycles: GI Control group (n=9); GII Sham pinealectomized rats (n=6); GIII Pinealectomized rats (n=ll). After two months, all animals in estrous phase were sacrificed and the ovary was removed and fixed in 10% formaldehyde. The material was processed by H.E. and Masson Trichrome. Besides analyzing of the morphology of the ovarian stroma, we calculated the maximum diameter of the interstitial cell nuclei. Results: The pinealectomized animals presented larger concentration of interstitial cells in the ovarian stroma. The histomorphometrical analyses revealed that the maximum diameter of the nuclei of the interstitial cells was much larger in pinealectomized rats than in the other groups. Conclusion: Our data suggest that larger metabolic activity and possibly larger hormonal production too could be taking place in these cells.
P4.17.08 IDENTIFICATION AND CHARACTERIZATION OF HUMAN 2OaHYDROXYSTEROID DEHYDROGENASE T. Nakaiima (l), M. Nishizawa (2), K Yasuda (l), S. Ito (2), H. Kanzaki (1) Dept OBIGYN, Kansai Medical University, Osaka, Japan (2) Dept Medical Chemistry, Kansai Medical University, Osaka, Japan Objective: 20a-hydroxysteroid dehydrogenase (HSD) belongs to aldoketo reductase (AKR) superfamily and catalyzes the reaction of progesterone to 20a-Hydroxyprogesterone, which is biological inactive form. Rat 20&-HSD gene was cloned and analyzed by human 20&-HSD was not. The aim of this study was to investigate human 20&-HSD to understand progesterone metabolism. Study Methods: genomic library by hybridization with rat 20&-HSD [AKRlC8] cDNA and performed high-stringency polymerase chain reaction (PCR) for hybridization positive clones with gene-specific primers. Four genes were isolated. We examined the expression of these genes by reverse transcription PCR in various human tissues and the substrate specificity using recombinant enzymes. Results: We isolated four aldo-keto reductase genes which shared high homology; human 20&-HSD [AKRlCl], bile acid-binding protein (BABP) {AKRlC2], prostaglandin F synthase (PGFS)[AKRlCS], and dihydrodiol dehydrogenase (DD) 4 [AKRlC4] genes. Human 20&HSD, BABP, and PGFS mRNAs were expressed ubiquitously, while DD4 mRNA was restricted in the liver. The four recombinant enzymes showed distinct substrate specificity. Conclusion: Human gene coding for the progesterone-metabolizing enzymes 20&-HSD was cloned. BABP, PGFS, and DD4 genes, which were highly homologous to 20&-HSD gene, were also cloned. The expression and the substrate specificity of these genes were elucidated.
P4.17.09 IMMUNOMORPHOLOGIC INVESTIGATION OF PUNCTURE BIOPSY SPECIMENS FROM WOMEN WITH PREVIOUS GESTOSIS L.E. J.G. Moisuk, I.M. Ilinsky, I.V. Sergeyko, F Baranova. Research Centre for Obstetrics, Gynecology & Perinatology, Moscow, Russia Objective: Gestosis is known to be a serious pregnancy complication with negative influence on maternal and perinatal outcomes. Also, chronic renal impairment is known as one of the causes of gestosis. We attempted to study immunomorphologic renal changes in women with previous gestosis. Metods: 20 women (mean age 32,0 + 0,4 years) who had had completed pregnancies ( 25% had one and 75% had two or more pregnancies) complicated by severe gestosis underwent renal biopsy performed 8 days 1,5 years later pregnancy completion. Immunomorphologic investigation of these specimens was done.