Effect of DNA damage of cumulus oophorus cells and lymphocytes analyzed by alkaline comet assay on oocyte quality and intracytoplasmic sperm injection success among patients with polycystic ovary syndrome.

AIM: Cumulus oophorus cells (COC) exhibit a close relationship with the oocytes. We aimed to determine the role of the DNA integrity of COC and lymphocytes on the oocyte and embryo quality and intracytoplasmic sperm injection (ICSI) success. METHODS: The COC obtained with the mechanical denudation of each oocyte and the lymphocytes obtained on oocyte retrieval day from 69 infertile polycystic ovary syndrome (PCOS) patients were used. The tail length, tail moment and tail DNA percentage were evaluated using an alkaline comet assay. The oocytes and embryos were graded. Clinical pregnancy was defined as the presence of a gestational sac with a beating heart. RESULTS: All of the DNA integrity parameters of the COC and lymphocytes were similar between the good and poor quality oocytes and between the good and poor quality embryos. There was no relationship between the DNA damage parameters and the fertilization and clinical pregnancy. The day 2 hormone levels, body mass index and age were negatively correlated with the DNA integrity parameters. No links were found between the embryo and oocyte scores and the DNA damage parameters. CONCLUSION: The DNA integrity of the COC and lymphocytes did not seem to be related to the oocyte and embryo quality and ICSI success.

Do follicular fluid gelatinase levels affect fertilization rates and oocyte quality?

BACKGROUND: Matrix metalloproteinase-2 and -9, known as gelatinases, are considered to be essential for tissue remodelling during the reproductive process. However, their role in reproduction is unclear. AIMS: In the present study, we aimed to investigate the relationship between follicular fluid gelatinase levels and oocyte quality and fertilization, and to compare the activities of gelatinase levels with different drug stimulation protocols. METHODS: We evaluated 60 women with unexplained infertility who underwent in vitro fertilization (IVF) treatment. Thirty patients underwent a gonadotropin-releasing hormone (GnRH) agonist protocol and 30 underwent a GnRH antagonist protocol. Follicular fluid was obtained during oocyte retrieval. Oocyte quality was determined using light microscopy, and oocytes were considered to be fertilized when two pronuclei were present. Gelatinase activities were measured using commercial enzyme-linked immunosorbent assay kits. The study was partially supported by the Scientific Research Unit of Suleyman Demirel University (Protocol Number: 3620-TU1-13), and all procedures were conducted with the approval of the Suleyman Demirel University Local Ethics Board. Statistical analyses of the data were performed using the independent t test, Fisher exact test, Mann-Whitney U test, one-way ANOVA, and posthoc least significant difference. RESULTS: Follicular fluid gelatinase levels were significantly higher for agonist drug administration (p = 0.001), and a positive correlation was observed between matrix metalloproteinase-9 levels and oocyte grade (p = 0.01). Moreover, a positive relationship between matrix metalloproteinase-9 levels and fertilization was observed (p = 0.02). CONCLUSION: Follicular fluid gelatinase activities, particularly MMP-9 activity, might be a predictor of oocyte quality and IVF success.

DNA methylation profiles of genes associated with angiogenesis in the samples of placenta in pregnancies complicated by intrauterine growth restriction.

BACKGROUND: Impairment in placental angiogenesis is blamed for the etiopathogenesis of intrauterine growth restriction (IUGR). AIM: To assess the genes related to angiogenesis in placental biopsies of pregnancies complicated by IUGR that could be aberrantly methylated and adversely affect placental angiogenesis. METHODS: The methylation profiles of soluble fms-like tyrosine kinase-1 (sFLT-1), vascular endothelial growth factor (VEGF), and the placental growth factor (PIGF) were evaluated using Illumina MiSeq™ System in placental biopsies from term IUGR pregnancies without preeclampsia (n = 18) and healthy controls (n = 17). DNA was isolated from samples of tissue collected from the fetal side of the placenta. In the targeted regions, we have identified 30, 24, and 29 CpG islands (CpGi) within sFLT-1, VEGF and PIGF genes, respectively. CpGi which are most methylated in the promoter regions of three genes were selected for the study from the database http://www.ensembl.org. RESULT(S): IUGR fetuses had significantly lower placental and fetal birth weight than controls. The promoter of sFLT-1 at three CpGi and VEGF at six CpGi were the regions with significant methylation differences between IUGR and control placentas. sFLT-1 was hypermethylated at 265 and 352 CpGi; however, hypermethylation was lower in IUGR group compared to control group at this position. sFLT-1 was hypomethylated at 456 CpGi in IUGR group and hypermethylated at the same region in control group. VEGF was hypomethylated at 668, 703, and 710 CpGi in control and IUGR groups; however, hypomethylation at these positions was significantly higher in control group compared to IUGR. 776, 845, and 863 CpGi of VEGF promoter were significantly hypermethylated in IUGR group whereas hypomethylated in control group. The methylation profile of PIGF did not differ between the groups. After adjustment for the factors known to affect fetal birth weight, DNA methylation of VEGF 668 CpGi had a significant negative association with fetal birth weight in the control and the IUGR group and a positive association with IUGR pregnancies. CONCLUSION(S): Our results do not support the hypothesis that altered DNA methylation in the placental angiogenic genes is a major mechanism generally involved in IUGR. Only a specific region (at 668 CpGi) corresponding to the promoter of VEGF may serve as an epigenetic marker of IUGR and may be involved in the mechanism of IUGR. Large sample-sized studies are needed to understand the effects of DNA methylation on placental gene function and how they might influence fetal growth.

The association of type D personality and depression with infertility in women.

Purpose: Type D personality-defined as the presence of two personality characters, namely negative affectivity (NA) and social inhibition (SI)-is associated with various disorders. The 14-item Type D Scale (DS14), which consists of NA and SI subscales, can be used for the detection of the presence of Type D personality. The aim of our study was to investigate the association of Type D personality and depression with infertility in women.Method: A total of 324 women, 168 primary unexplained infertile women (92 patients undergoing in vitro fertilization (IVF) treatment and 76 undergoing intrauterine insemination (IUI) treatment) and 156 fertile controls were recruited. The 21-item Beck Depression Inventory (BDI-21) and DS14 were completed by all participants. The study was approved by Local Ethics Committee with the protocol number 72867572-050-218.Results: Depression and Type D personality were found to be significantly more prevalent in the infertile group than the fertile group. Type D was positively associated with infertility (OR = 2.34, 95% CI = 1.45-3.78, p < .0001), especially in the younger-aged (<35 years) population (OR = 2.59, 95% CI = 1.48-4.5, p = .001). After adjusting for the duration of marriage, age, obesity, educational level, and the same characteristics of the partner, the association between Type D personality and infertility persisted (OR = 2.56, 95% CI = 1.52-4.29, p < .001). The scores of the BDI-21 and NA subscale were found to be negatively correlated with age and partner's age. The BDI and SI scores, and the NA, SI, and Type D personality rates were similar between the IUI and the IVF groups; however, the NA score was higher, and depression was found to be more prevalent and severe in the IUI group than the IVF group.Conclusions: Type D personality could be positively associated with infertility, especially in younger-aged women.

Thrombin activatable fibrinolysis inhibitor and other hemostatic parameters in patients with polycystic ovary syndrome.

OBJECTIVES: To investigate the plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in women with polycystic ovary syndrome (PCOS) and its correlation with various metabolic, hormonal and hemostatic parameters. METHODS: Forty-eight women with PCOS and 43 age- and BMI-matched ovulatory controls were recruited during a 20-month study period. Blood samples were drawn for all tests, which included plasma lipids and lipoproteins, reproductive hormones, glucose, insulin, TAFI antigen concentration, plasminogen activator inhibitor-1 (PAI-1) activity, fibrinogen concentration, thrombomodulin, thrombin-antithrombin (TAT) complexes, D-dimer, Protein C Antigen, Protein S Antigen, Antithrombin III (AT III) and activated protein C (APC) resistance. RESULTS: Plasma TAFI levels of PCOS patients were found to be significantly higher than in healthy controls (93.8%+/-30.6%vs. 79.8% +/- 22.4%, p < 0.05). Plasma levels of D-dimer, AT III, PAI-1 and thrombomodulin were also significantly higher in women with PCOS compared with healthy controls. All the other hemostatic parameters (including TAT complexes; Protein C; APC; and Protein S) were comparable between the two study groups. CONCLUSION: This study showed that plasma levels of TAFI, PAI-1, D-dimer, AT III and thrombomodulin were significantly increased in women with PCOS compared with age- and BMI-matched controls.

Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy.

Leukemia inhibitory factor (LIF) is essential for implantation of the embryo in the endometrium. It is not clear whether the blastocyst requires expression of LIF for implantation into tissues other than endometrium. Immunohistochemical localization of LIF was performed in the fallopian tube of 20 women with ectopic pregnancies, 7 women with normal pregnancies and 20 healthy non-pregnant women. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and non-pregnant fertile women or at operation for tubal surgery in ectopic pregnancies. Biopsies were assayed by immunohistochemistry. Semi-quantitative immunohistochemical reaction scores (IRS) were used for immunohistochemical analyses. Immunolabeling of LIF was detected in the surface epithelium and stroma of fallopian tubes in all subjects. IRS score in the epithelium and stroma of non-pregnant women and women with intrauterine pregnancy were similar (p>0.05). However, women with ectopic pregnancy had significantly increased labeling of LIF compared to others (p<0.05). Immunohistochemical labeling of LIF in the fallopian tube was found to be increased in ectopic pregnancies compared to non-pregnant and healthy pregnant controls. This may indicate a role of LIF in the ectopic implantation of embryos.

Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation in rats: role of vitamins E and C.

Fluoride is a strong, hard anion and cumulative toxic agent. The effect of fluoride intoxication on lipid peroxidation in endometrial tissue and the protective effects of combinations of vitamins E and C in rats were studied. Additionally, the apoptotic changes in endometrial tissue were examined. Experimental groups were as follows: control group; a group treated with 100 mg/l fluoride (F group); and a group treated with 100 mg/l fluoride plus vitamins E and C (F+Vit group). The F and F+Vit groups were treated orally with fluoride for 30 days. Vitamins E and C were injected simultaneously at doses of 50 mg/kg day i.m. and 20 mg/kg day body weight i.p. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick and labeling (TUNEL) method. Malondialdehyde (MDA) levels were determined in uterine tissue of rats. Fluoride caused a significant increase in MDA levels (an important marker of lipid peroxidation) in the fluoride group compared with the controls (p<0.05). Vitamins E and C significantly reduced the fluoride-induced lipid peroxidation in the F+Vit group compared with the F group (p<0.05). Diffuse apoptosis in glandular epithelium and stromal cells was found in endometrial tissues of F treated rats by TUNEL method. The severity of these lesions was reduced by the administration of vitamins. From these results, it can be concluded that subchronic fluoride administration causes endometrial apoptosis, and lipid peroxidation may be a molecular mechanism involved in fluoride-induced toxicity. Furthermore, treatment with a combination of vitamins E and C reduced endometrial apoptosis caused by fluoride.

Ovarian toxicity in rats caused by methidathion and ameliorating effect of vitamins E and C.

We have investigated the effect of subchronic administration of methidathion (MD) on ovary evaluated ameliorating effects of vitamins E and C against MD toxicity. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD + Vit group). MD and MD + Vit groups were given MD by gavage five days a week for four weeks at a dose level of 5 mg/kg/day by using corn oil as the vehicle. Serum malondialdehyde (MDA: an indicator of lipid peroxidation) concentration, serum activity of cholinesterase (ChE), and ovary histopathology were studied. The level of MDA increased significantly in the MD group compared with the control (P < 0.005). Serum MDA decreased significantly in the MD + Vit group compared with the MD group (P < 0.05). The activities of ChE decreased significantly both in the MD and MD + Vit groups compared with the controls ( P < 0.05). However, the decrease in the MD + Vit groups was less than in the MD group; the ChE activity in the MD + Vit group was significantly higher compared with MD group (P < 0.05). Number of ovarian follicles were significantly lower in the MD group compared to the controls (P < 0.05). Number of atretic follicles were significantly higher in the MD group than in the controls (P < 0.05). Follicle counts in MD + Vit group showed that all types of ovarian follicles were significantly higher, and a significant decrease in the number of atretic follicles compared with the MD group (P < 0.05). In conclusion, subchronic MD administration caused an ovarian damage, in addition, LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Treatment with vitamins E and C after the administration of MD reduced LPO and ovarian damage.

Protective effect of caffeic acid phenethyl ester (CAPE) on fluoride-induced oxidative stress and apoptosis in rat endometrium.

High fluoride intake may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the tissues, thus leading to oxidative damage. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygen species mediated oxidative stress in ischemia-reperfusion and toxic injuries. Several studies suggest that supplementation with anti-oxidant can influence fluoride induced tissue damage. The aims of this study was to investigate the possible role of malondialdehyde (MDA) levels and activity of superoxide dismutase (SOD) and catalase (CAT), in the pathogenesis of fluoride-induced endometrial damage and to demonstrate the effect of CAPE, the potent antioxidant, in decreasing the toxicity. Twenty-four adult female rats were randomly divided into three experimental groups, as follows: control group, fluoride-treated group (F), and fluoride plus CAPE-treated group (F+CAPE). Fluoride was given orally as 30mg/L NaF solution in spring water daily for 45 days. CAPE was co-administered intraperitoneally (i.p.) with a dose of 10µM/(kgday) for 46 days. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. The activities of antioxidant enzymes such as SOD and CAT as well as the concentration of MDA, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the endometrium. Fluoride administration increased MDA levels (p<0.05), decreased SOD (p<0.05) and CAT (p<0.05) activities. CAPE co-administration with fluoride treatments caused significantly decreased MDA levels (p<0.05), increased SOD (p<0.05) and CAT (p<0.05) activities in endometrial tissue when compared with F alone. Diffuse apoptosis in glandular epithelium and stromal cells was found by TUNEL method in endometrial tissues of rats treated with fluoride. The severity of these lesions was reduced by administration of CAPE. In conclusion, our study demonstrated that MDA may play an important role in the pathogenesis of fluoride-induced oxidative endometrial damage. CAPE may have protective aspects in this process by its antioxidant and anti-inflammatory effect.

Evaluation of caspase-dependent apoptosis during methyl parathion-induced endometrial damage in rats: Ameliorating effect of Vitamins E and C.

The role of reactive oxygen species (ROS) in various diseases of the female reproductive tract has been shown, and oxidative stress is an important component of the mechanism of toxicity of OPIs. Methyl parathion (MPT) is one of the most widely used organophosphate insecticides (OPIs) in agriculture. The aim of the study was to elucidate the effect of subchronic MPT exposure on lipid peroxidation and serum activities of cholinesterase (ChE), and the protective effects of combination of antioxidant Vitamins E and C in rats. Additionally, histopathological and immunohistochemical changes in endometrium were aimed to be examined. Three groups of rats were used in the experiment. The first group was treated with 5mg/kg MPT; the second group was treated with 5mg/kg body weight MPT plus Vitamin E and Vitamin C (MPT+Vit); and the third group was given only corn oil (control). MPT and MPT+Vit groups were given MPT by gavage 5 days a week for 4 weeks at a dose level of 4mg/(kgday) by using corn oil as the vechicle. Vitamins E and C were injected at doses of 50mg/kg i.m. and 20mg/kg body weight i.p. Histopathological and immunohistochemical examinations for caspase-3 and caspase-9 were accomplished in the endometrium. The level of malondialdehyde (MDA) increased significantly in the MPT group compared with the control group (p<0.05). MDA significantly decreased in the MPT+Vit group compared with the MPT group (p<0.05). Administration of Vitamins E and C along with MPT significantly reduced the histopathological changes and the extent of apoptosis. In conclusion, subchronic MPT administration caused endometrial damage and that treatment with a combination of Vitamins E and C reduced endometrial damage caused by MPT.

Efficacy of intrauterine lidocaine for removal of a "lost" intrauterine device: a randomized, controlled trial.

OBJECTIVE: To evaluate the efficacy of intrauterine lidocaine instillation in reducing patient discomfort during the removal of a "lost" intrauterine device (IUD). METHODS: This double-blinded, randomized, placebo-controlled trial included 68 women who underwent removal procedure for a "lost" IUD. Thirty-four women were allocated to the lidocaine group and 34 to the saline group. The main outcome measure was the intensity of pain during, immediately after, and 20 minutes after the procedure, assessed by a visual analog scale. Statistical analysis was performed using the Friedman test with Bonferroni correction, Student t test, and chi2. RESULTS: There were no statistically significant differences between the study group and the control group in mean age, parity history of chronic pelvic pain and dysmenorrhea, history of curettage, education, socioeconomic status, menopausal status, breastfeeding, type of IUD, and duration of IUD. Pain scores demonstrated a significant difference between groups during the procedure (placebo 6.41 +/- 1.15, lidocaine 5.23 +/- 0.69, P < .01), immediately after procedure (placebo 6.05 +/- 1.01, lidocaine 4.94 +/- 0.60, P < .01), and 20 minutes after procedure (placebo 4.32 +/- 0.63, lidocaine 4.44 +/- 0.66, P < .01). The number needed to treat was 3 (95% confidence interval 2-9). CONCLUSION: Intrauterine lidocaine appears to be effective in decreasing pain in women undergoing the removal procedure of a "lost" IUD. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT00308841. LEVEL OF EVIDENCE: I.

Influence of electromagnetic fields and protective effect of CAPE on bone mineral density in rats.

BACKGROUND: Most mobile phones emit electromagnetic radiation at 900 MHz or 1800 MHz. An electromagnetic field has some biological effects on the behavior of the cell population of bone. The aim of this work is to evaluate the effects of the radiation emitted by mobile phones on bone mineral density (BMD). The effects of caffeic acid phenethyl ester (CAPE) on the radiation-induced changes were also investigated. METHODS: In the study, 48 Sprague Dawley rats were used. Rats were divided into five groups as follows: control, irradiated with 900 MHz, irradiated with 900 MHz and treatment, irradiated with 1800 MHz, irradiated with 1800 MHz and treatment groups. The rats in the control group (first group) were left within the experimental setup during 30 min/day for 28 days without radiation exposure. Nine hundred-MHz radiation group was exposed to irradiate both second and third groups for 28 days (30 min/day); 1800-MHz radiation group was exposed to irradiate both fourth and fifth groups for 28 days (30 min/day). Third and fifth groups were also treated by CAPE for 28 days. Treatment groups received 10 microml/kg/day CAPE i.p. before the irradiation. Bone mineral densities were determined in all groups. RESULTS: BMD was found to be decreased in the irradiated groups and to be increased in the treatment groups. CONCLUSIONS: The changes were not significant (p >0.05).

Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating effect of antioxidant vitamins E and C.

We aimed to investigate the effect of subchronic administration of dichlorvos (DDVP) on endometrium and to evaluate ameliorating effects of a combination of Vitamins E and C against DDVP toxicity in the rat. Three groups of rats were used in the experiment. The first group was treated with 4 mg/kg DDVP; the second group was treated with 4 mg/kg body weight DDVP plus Vitamins E and C (DDVP+Vit); the third group was given only corn oil (control). DDVP and DDVP+Vit groups were given DDVP by gavage 5 days a week for 4 weeks at a dose level of 4 mg/kg day by using corn oil as the vechicle. Vitamins E and C were injected at doses of 50 mg/kg i.m. and 20 mg/kg body weight i.p. Histopathological and immunohistochemical examinations for caspase-3 and caspase-9 were accomplished in the endometrium. The level of malondialdehyde (MDA) increased significantly in the DDVP group compared with the control group (p<0.05). MDA significantly decreased in the DDVP+Vit group compared with the DDVP group (p<0.05). Administration of Vitamins E and C along with DDVP significantly reduced the histopathological changes and the extent of apoptosis. In conclusion, subchronic DDVP administration caused endometrial damage and that treatment with a combination of Vitamins E and C reduced endometrial damage caused by DDVP.

Endometrial apoptosis induced by a 900-MHz mobile phone: preventive effects of vitamins E and C.

Numerous reports have described the effects induced by an electromagnetic field (EMF) in various cellular systems. The purposes of this study were to examine oxidative stress that promotes production of reactive oxygen species induced by a 900-megahertz (MHz) mobile phone and the possible ameliorating effects of vitamins E and C on endometrial tissue against EMF-induced endometrial impairment and apoptosis in rats. Animals were randomly grouped as follows: (1) sham-operated control group (n=8), (2) 900 MHz EMF-exposed group (n=8; 30 min/d for 30 d), and (3) 900 MHz EMF-exposed group, treated with vitamins E and C (n=8; 50 mg/kg intramuscularly and 20 mg/kg body weight intraperitoneally before daily EMF exposure). Malondialdehyde (an index of lipid peroxidation) was used as a marker of oxidative stress-induced endometrial impairment; Bcl-2, Bax, caspase-3, and caspase-8 were assessed immunohistochemically. In this study, increased malondialdehyde levels in endometrial tissue and apoptosis illustrated the role of the oxidative mechanism induced by exposure to a 900-MHz mobile phone-like device and vitamins E and C; via free radical scavenging and antioxidant properties, oxidative tissue injury and apoptosis were ameliorated in rat endometrium. In conclusion, exposure to 900-MHz radiation emitted by mobile phones may cause endometrial apoptosis and oxidative stress, but treatment with vitamins E and C can diminish these changes and may have a beneficial effect in preventing endometrial changes in rats.

Magnetic resonance imaging for stress incontinence: evaluation of patients before and after surgical correction.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of magnetic resonance imaging (MRI) in the pre and postoperative assessment of stress urinary incontinence. METHODS: Fifteen female patients with clinical evidence of stress urinary incontinence were included in this prospective study. All the patients underwent MRI in the supine position both preoperatively and postoperatively. For imaging, we used a 1.0 T magnet, T2-weighted images were obtained in the midline sagittal plane with patients at rest. Images were evaluated for anatomical stress urinary incontinence alterations, such as the increased distance between the pubococcygeal line and the bladder base and the posterior urethro-vesical angle and the urethral inclination angle changes. Wilcoxon signed rank test allowed comparisons of pre and postoperative results. RESULTS: Compared with postoperative measurements, the bladder base was lowered significantly by an average of 9.4+/-4.0 mm (P<0.01), posterior urethro-vesical angle was significantly increased by an average of 127.8+/-11.4 degrees (P<0.01), and the urethral inclination angle was significantly increased by an average of 54.9+/-10.1 degrees (P<0.01) preoperatively. CONCLUSION: Our results suggest that MRI can play a major role in the preoperative and postoperative assessment of stress urinary incontinence. It can reliably detect anatomical urinary incontinence alterations. MRI should be considered in failed surgery, complex prolapse, and in differentiating genuine stress incontinence resulting from malposition of the bladder neck from stress incontinence due to intrinsic urethral damage.

The effect of sodium monofluorophosphate therapy on lipid and lipoprotein metabolism in postmenopausal women.

OBJECTIVE: To investigate the effect of a low dose of fluoride, combined with hormone replacement therapy (HRT) or alone, on serum lipids and lipoproteins in postmenopause. STUDY DESIGN: One hundred and thirty-five healthy postmenopausal women were enrolled in this prospective study and randomly assigned to: (1) oral monofluorophosphate (MFP, 25 mg per day); or (2) HRT (a combination of oral conjugated estrogen 0.625 mg in conjunction with medroxyprogesterone acetate 5 mg daily); or (3) HRT + MFP; or (4) placebo, for 18 months. Serum lipid and lipoprotein levels were measured at enrollment and at the end of the study period. RESULTS: Total cholesterol was not significantly different among groups, with a decrease in the HRT and the HRT + MFP groups (respectively, -7.8 and -7.9%), and a small increase in the MFP group (0.4%). LDL-C did not differ significantly in the groups, with a decrease in the HRT and HRT + MFP groups (respectively, -10.3 and -10.4%), and a slight increase in the MFP group (0.8%). TG decreased with -12 and 11.8% in the HRT and HRT + MFP groups (P = 0.052 and 0.055, respectively), but a slight increase was seen in the MFP group (1.4%). For HDL-C, both HRT and HRT+MFP groups showed a small increase (respectively, 3.5 and 3.6%), whereas MFP group showed a slight decrease (-0.9%, NS). CONCLUSION: We conclude that long-term use of a low dose of fluoride had no significant adverse changes in the lipid and lipoprotein profile in postmenopause. It neither attenuated nor potentiated the effect of HRT on lipids and lipoproteins.

Relationship between bone scintigraphy and tumor markers in patients with breast cancer.

PURPOSE: The aim of this study is to specify the precise role of bone scintigraphy and serum CEA and CA 15-3 assays in the monitoring of breast cancers in order to optimize their use and to determine whether it is possible to guide the prescription of bone scan by the use of CEA and CA 15-3 assays in the monitoring of breast cancer. METHODS: For this purpose, from November 1997 to May 2002, 98 consecutive female breast cancer patients (median age, 52 years; range 35-77 years) underwent bone scintigraphy during follow-up. In these patients values of tumor markers were compared with the results of bone scintigraphy. Some of the patients with bone metastasis were checked repeatedly at intervals of 6 to 12 months, resulting in 49 patients with bone metastasis and 74 patients without bone metastasis being included in the study. RESULTS: In patients with bone metastasis, serum CEA levels were abnormal in 23/49 cases and CA 15-3 serum concentrations were elevated above the cut-off in 33/49 cases. Among patients without bone metastasis, CEA and CA 15-3 serum concentrations were normal in 50/74 and 55/74 cases respectively. The combination of the two markers improved the diagnostic sensitivity. CONCLUSION: Although serial tumor marker measurements are an efficient and cost effective method of monitoring disease progression, it does not allow prediction of the bone scan results; so it is not justifiable to reject a bone scintigraphy on the basis of these markers.

Influence of NaMFP therapy on plasma leptin concentration in postmenopausal women.

OBJECTIVE: To investigate the effect of a low dose of fluoride on the plasma leptin concentration in postmenopausal women. STUDY DESIGN: One hundred one healthy, postmenopausal women participated in this comparative study. To evaluate the influence of NaMFP treatment and body mass index (BMI) on leptin concentrations, patients were allocated to one of four groups: postmenopausal women (1) on NaMFP with BMI < 25 (n = 29), (2) on NaMFP with BMI > or = 25 (n = 26), (3) not on NaMFP with BMI > or = 25 (n = 24) and (4) not on NaMFP with BMI < 25 (n = 22). Plasma leptin levels were measured before and 12 months after the initiation of NaMFP or, in groups 3 and 4, after the start of the study. Ninety-eight women completed the study. RESULTS: There were significant differences in leptin concentrations at baseline and 12 months between NaMFP users with BMI > or = 25 and BMI < 25 and between women not taking NaMFP with BMI > or = 25 and BMI < 25 (group 2 versus 1 and 3 versus 4). After controlling for BMI, the use of NaMFP was not found to be related to the leptin value (group 1 versus 4 and group 2 versus 3). Although plasma leptin concentrations tended to be decreased slightly at 12 months in NaMFP users, this decrease was not statistically significant (P = .065). CONCLUSION: Leptin concentrations are significantly higher in obese, postmenopausal women than in nonobese, postmenopausal women. Plasma leptin concentrations are slightly but nonsignificantly influenced by long-term, low-dose fluoride treatment. Further studies are needed to elucidate the role of NaMFP on plasma leptin concentrations.

Effects of menopause on bone mineral density in women with endemic fluorosis.

PURPOSE: The effects of menopause on bone mineral density (BMD) in women with endemic fluorosis were investigated. MATERIALS AND METHODS: Eighty healthy Turkish women who lived in and around the city of Isparta were selected randomly and enrolled in this study. They were separated into four groups: group 1, 20 premenopausal women with regular menstrual cycles and endemic fluorosis; group 2, 20 postmenopausal women with endemic fluorosis; group 3, 20 premenopausal normal women constituting one control group; and group 4, 20 postmenopausal normal women constituting the other control group. Bone mineral density was measured in the lumbar spine and proximal femur using dual-energy x-ray absorptiometry. RESULTS: In the premenopausal group, BMD values of vertebrae L2-L4 and Ward's triangle in women with endemic fluorosis were significantly greater than the respective values in women without endemic fluorosis (P = 0.024, P = 0.036). There were no differences between the groups in BMD values of the femoral neck (P = 0.156) and intertrochanteric area (P = 0.076). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward's triangle in the postmenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women without endemic fluorosis (P < 0.001, P = 0.015, P = 0.002, and P < 0.001, respectively). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward's triangle in the premenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women with endemic fluorosis (P = 0.010, P = 0.002, P = 0.004, and P = 0.010, respectively). The BMD values of the sites noted for the premenopausal controls were significantly greater than those of postmenopausal controls (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: Postmenopausal BMD values in both endemic fluorosis and controls were significantly less than premenopausal BMD values. Although the differences were less prominent in women with endemic fluorosis, menopause is still the major determinant of BMD in the spine and femur.

Neuroprotective effects of raloxifene on experimental spinal cord injury in rats.

INTRODUCTION: The aim of this study was to evaluate the possible beneficial effect of raloxifene on cytokine production and ultrastructure of the spinal cord after spinal cord injury (SCI) in an animal model. METHODS: Forty-eight male, adult Wistar Albino rats were divided into 4 groups for this study: A (only laminectomy), B (trauma; laminectomy + spinal trauma), C (raloxifene group; laminectomy + spinal trauma + raloxifene treated) and D (vehicle group; laminectomy + spinal trauma + vehicle treated). SCI was achieved by compression of the spinal cord horizontally and extradurally for 1 minute with an aneurysm clip (Sugita no: 07-934-11, closing pressure of 1.37-1.72 N). Spinal cords were extirpated at T7-T12 level, and tissue samples of the spinal cord samples were gathered for tumor necrosis factor α (TNF-α)/protein and interleukin (IL)-1ß/protein measurements at first and sixth hours. Spinal cords harvested at sixth hour were evaluated for ultrastructural changes. RESULTS: Both TNF-α/protein and IL-1ß/protein levels in the samples harvested 6 hours after surgery in the group B (62.70 ± 6.67 pg/mg and 11.25 ± 1.37 pg/mg, respectively) were higher than those taken from group A (P = 0.002 and P = 0.041, respectively). Furthermore, TNF-α/protein and IL-1ß/protein levels in the samples of animals treated with raloxifene (23.27 ± 5.27 pg/mg and 6.09 ± 0.77 pg/mg, respectively) were significantly lower than those taken from group B (P = 0.002 and P = 0.002, respectively). In the trauma group, electron microscopic examinations revealed deformities inside the cells and severe edema in neuropil. Raloxifene seemed to attenuate these ultrastructural changes at sixth hour after SCI. CONCLUSION: A single dose of 3.0 mg/kg of raloxifene intraperitoneally given 30 minutes after the induction of SCI reduced the production of TNF-α and IL-1ß 6 hours after SCI and attenuated ultrastructural changes in a rat model.