c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer.

PURPOSE: To evaluate the expression of c-kit (CD117) in endometrial hyperplasia and endometrial cancer. METHODS: Expression of c-kit in 10 normal endometrium, 18 simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by immunohistochemistry. RESULTS: c-Kit expression decreased as the lesion progressed to endometrial cancer. Immunostaining was mostly focal and weak in the normal endometrium and was mostly diffuse and strong in the simple and complex endometrial hyperplasia. CONCLUSIONS: Simple and complex hyperplastic endometrial tissues express diffuse cytoplasmic staining for c-kit and the expression decreases with the progression of the lesion.

An appraisal of serum preptin levels in PCOS.

Plasma preptin levels were higher in women with PCOS compared with the control group (mean±SD, 823.2±140.7 vs. 324.9±147.3 pg/mL). This article suggests a potential role of preptin in the pathogenesis of PCOS.

Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in PCOS.

The aim of this study was to establish the frequency of angiotensin-converting enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with polycystic ovary syndrome (PCOS) and to examine the association of this polymorphism with insulin resistance. A total of 32 women with PCOS and 31 healthy, age- and body mass index-matched controls were studied. Serum lipids, fasting glucose, insulin and other hormones concentrations were measured. Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR). DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D polymorphism was carried out by polymerase chain reaction. ACE genotypes were distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in four (12.9%) of healthy subjects. The frequency of D and I alleles were found in 69% and 31% of the PCOS group and 55% and 45% in the control group, respectively. There were no significant differences regarding the genotypic distribution and allelic frequency between the groups. However the ACE DD genotype was significantly associated with serum insulin concentrations and HOMA-IR measurement (both P=0.005). ACE DD genotype is associated with an increased insulin resistance in women with PCOS.

Effects of highly purified urinary FSH and human menopausal FSH on uterine myoelectrical dynamics.

The aim of the study was to investigate the effects of urinary follicle-stimulating hormone (FSH) compounds on the electrical activity of myometrium using signal-processing techniques. Thirty animals were involved in the experiment. After two successive normal estrous cycles, 15 of these animals were put into three equal subgroups. Group 1 was the control; animals were given solvent. Groups 2 and 3 were treated with Urofollitropin and Menotropin, respectively. The other 15 animals were ovariectomized and subjected to the same protocol. Their uterine myoelectrical signals were recorded over a period of at least 3 min at a sampling frequency of 500 Hz, and analyzed through software assisted signal processing. The results show the power and some characteristic spectral components of myoelectrical signal were differentially reduced with the administration of highly purified urinary FSH and human menopausal FSH but significant differences were not detected between their histology. In conclusion, uterine myoelectrical signals change with administration of urinary FSH preparations. Human menopausal FSH and more precisely highly purified FSH suppress the spectral components and modify the power of the myoelectrical signals which provides uterine quiescence.

Virtual hysterosalpingography and hysteroscopy: assessment of uterine cavity and fallopian tubes using 64-detector computed tomography data sets.

Hysterosalpingography is the primary technique in providing coarse information on the morphology of endometrial cavity and fallopian tubes. In this preliminary study, 64-detector computed tomography was used for three-dimensional imaging of endometrium and fallopian tubes.

Enhanced endometrial response to a magnetic intrauterine device: a preliminary study.

OBJECTIVE: To evaluate the effects of an intrauterine device producing a static magnetic field on the endometrial histology of rats. METHODS: The experiments involved 20 adult female Wistar albino rats that were divided into five groups. Group 1 was sham-operated; Groups 2, 3 and 4 had a copper intrauterine device (IUD), an uncovered intrauterine magnet (IUM) or an intrauterine silicone-coated IUM, respectively, inserted into one of the uterine horns; in Group 5 an uncovered IUM was implanted subcutaneously. Six days later the rats were sacrificed; endometrial and subcutaneous tissues were harvested and examined microscopically. RESULTS: Copper IUDs caused classical cellular infiltration through the endometrium. IUMs, producing a static magnetic field, also caused leucocyte and monocyte infiltration of the endometrium and, in addition, a significant leucocyte accumulation over the endometrial surface. CONCLUSION: This preliminary study reveals that an intrauterine magnet induces the accumulation of leucocytes in the uterine cavity in addition to the classic stromal infiltration caused by commercially available nonmagnetic IUDs. This activity could contribute to a greater efficacy of intrauterine contraception and should be investigated further.

Use of porcine small intestinal submucosa to reconstruct an ovarian defect.

OBJECTIVE: To investigate the feasibility of using porcine small intestinal submucosa (SIS) as a scaffold for repairing ovarian defects. METHOD: Fourteen female New Zealand rabbits undergoing ovarian resection were randomly allocated to 2 equal groups. The unilateral ovarian defects were repaired with SIS in group 1 animals and without SIS in group 2 animals (control). The volumes of the ovaries were calculated and the severity of adhesions was assessed in 1 animal from each group each month. The ovaries were removed and examined under a microscope. RESULTS: The volumes of the SIS-grafted ovaries were larger than those of the operated ovaries of the control animals (P<0.05). The SIS-grafted ovaries had a lower adhesion score than the operated ovaries of the control group (P<0.001). SIS grafts showed hemorrhage and leukocyte infiltration until the 4th week after surgery, but the ovarian tissue appeared to be well organized from the 12th to the 16th week. At the 28th week, primordial follicles were scattered in the SIS graft. CONCLUSION: SIS graft could be used for repairing the ovary after surgery.

Microstructural changes in uterine leiomyomas and myometrium: a diffusion-weighted magnetic resonance imaging study.

Although morphological and histopathological changes in uterine leiomyomas have been investigated in detail, the microstructural disruptions could not be studied in the living organism. Diffusion-weighted magnetic resonance imaging (DWI) is a novel tool to assess microstructural changes in vivo. The aim of this study was to investigate and characterize the diffusional property of leiomyomatous tissues with DWI. Sixteen females with a total of 21 leiomyomas were imaged with a 1.5-tesla clinical MR scanner. DWI images of leiomyomas, adjacent myometrial and myometrial tissues of healthy controls were obtained and quantified using apparent diffusion coefficient (ADC) maps. Mean ADC values of these groups were 1,201, 1,684, 1,661 mm(2)/s x 10(-6), respectively. ADC values in leiomyomas were significantly lower than those observed in the myometrium (p < 0.001). Cut-off values produced 91% sensitivity and 100% specificity. As ADC values implied the presence of cytotoxic edema in leiomyomas, the technique was found to be promising in observing temporal variations in leiomyomas and to monitor even the most subtle effects of therapeutic interventions.

Combating endometriosis by blocking proteasome and nuclear factor-kappaB pathways.

BACKGROUND: The objective of this study is to investigate the effect of pyrrolidine dithiocarbamate [PDTC; a nuclear factor-kappaB (NF-kappaB) inhibitor] and bortezomib (Velcade; a proteasome inhibitor) on the development of experimental endometriotic implants in rats. METHODS: Endometriosis was surgically induced in 30 rats using the method of Vernon and Wilson. Three weeks later the viability and volume of the implants were recorded and classified. Afterwards, rats were put into three groups with equal numbers. The groups were labelled as the control, the PDTC and the bortezomib groups. Seven days after treatment, a third laparotomy was done and the volume of implants was measured again. The animals were then sacrificed, and the implants were stained with Ki67, proliferating cell nuclear antigen (PCNA), CD34, CD31 and Masson's trichrome histochemical staining. RESULTS: In 80% of the implanted rats, vesicles at the suture region were observed, and the rats graded according to average vesicle diameter (D) as: Grade 1 (no vesicle, 20% of rats), Grade 2 (D < 2 mm, 33.3% of rats), Grade 3 (2 mm 4.5 mm, 26.7% of rats) and Grade 4 (D > 4.5 mm, 20% of rats). After treatment with PDTC or bortezomib, these percentages were decreased for Grades 3 and 4, and increased in Grade 1. The post-treatment implant volumes were decreased in the PDTC and bortezomib groups (P < 0.002 and P < 0.001), and slightly increased in the control group (P = 0.279). In the PDTC and bortezomib groups, CD34, CD31, PCNA and Ki67 expression levels were similar but were significantly reduced compared with the control group. CONCLUSIONS: PDTC and bortezomib may represent a novel therapeutic strategy for treatment of endometriosis.

Spectrotemporal changes in electrical activity of myometrium due to recombinant follicle-stimulating hormone preparations follitropin alfa and beta.

OBJECTIVE: To investigate the effects of follitropin alfa and beta on the myoelectrical activity of rat myometrium using signal-processing techniques. DESIGN: Prospective, placebo-controlled study. SETTING: Animal and pharmacology laboratory at Inonu University. ANIMAL(S): Forty-five female Wistar albino rats. INTERVENTION(S): Thirty of 45 animals involved in the experiment were registered as the superovulation group. After two successive normal estrous cycles, these animals were put into three equal subgroups. Group 1 was the control; animals were given 0.9% saline. Groups 2 and 3 were treated with follitropin alfa (Gonal-f) and follitropin beta (Puregon), respectively. The other 15 animals were ovariectomized (OVX) and subjected to the same protocol. The uterine myoelectrical signals were recorded and analyzed using a Matlab environment. MAIN OUTCOME MEASURE(S): Power/second, variance, and the effects of recombinant human follicle-stimulating hormone (FSH) on myoelectrical signals were assessed through temporal, spectral, and joint time-frequency analysis. The uterine endometrium and ovarian morphology were also assessed concerning primary follicles, antral follicles, and corpora lutea. RESULT(S): The power and some characteristic spectral components of myoelectrical signal were reduced with the administration of follitropin alfa and beta. No statistically significant difference was detected between endometrial and ovarian histology of the rats treated with these follitropins. CONCLUSION(S): Uterine myoelectrical signals change with administration of recombinant human FSH preparations. Follitropin beta and, more precisely, follitropin alfa suppress the spectral components and power of the myoelectrical signals, which provides uterine quiescence.

Novel noninvasive detection method for endometriosis: research and development of scintigraphic survey on endometrial implants in rats.

In this experimental study on endometriosis, the majority of the implants were successfully detected with technetium-(99mTc) labeled red blood cell scintigraphy.

Assessment of myoelectrical signal parameters in estrogen, progesterone, and human chorionic gonadotropin administered in nonpregnant rat myometrium after ovariectomy.

OBJECTIVE: To investigate the correlation of myoelectrical signals with spontaneous contractile events and physiological states in the nonisolated uterine horn of rats. DESIGN: In vivo uterine myoelectrical activity recording study. SETTING: Animal and pharmacology laboratory at Inonu University. ANIMAL(S): Thirty-six female Wistar albino rats. INTERVENTION(S): Six animals were not castrated and served as a sham-operated control group; the other 30 were ovariectomized (OVX) and put into groups: unbiased OVX subjects, estrogen (E)-biased OVX subjects, P-biased OVX subjects, E-plus-P-biased OVX subjects, and hCG-biased OVX subjects. An MP100 A-CE was used for data acquisition, and a personal computer was used for processing. MAIN OUTCOME MEASURE(S): Besides the temporal, spectral, and joint time-frequency (spectrotemporal) analysis, some quantitative measures such as standard deviation and mark to space power ratios of myoelectrical signals were measured. RESULT(S): Progesterone, E, and hCG administration down-regulated the power and contraction frequency of the uterine electrical signal. The spectral concentrations that occurred around the 0.9, 0.35, and 0.7 Hz frequency ranges may be distinguishing characteristics for P, E, and hCG, respectively. CONCLUSION(S): Based on the obtained results, uterine contractions change with ovariectomy and administration of hormones. Progesterone, E, and hCG particularly prolong the quiescent periods of the uterus by reducing the frequency of uterine contractions as well as the power of the myoelectrical activity. Individual or combined use of P, E, or hCG might favor quiescence of the uterine muscle and the maintenance of pregnancy.

Pure uterine lipoma.

Lipomatous tumors of the uterus are unusual, benign neoplasms seen in postmenopausal women. Although many of the mixed-type cases such as lipoleiomyoma and fibrolipoma have been reported, pure uterine lipomas are extremely rare. In the literature, a few cases with pure uterine lipoma have been reported. We first present the advanced magnetic resonance findings of pure uterine lipoma, followed by those of ultrasonography (US) and computed tomography (CT). We markedly detected lipid peaks on the magnetic resonance spectroscopy (MRS) and the apparent diffusion coefficient value to be 0.00 due to chemical-shift effects with diffusion-weighted imaging (DWI). Although pelvic lipomatous tumors can be diagnosed with US and CT, in some cases, further workup may be required to localize the lesion. MRI may yield more valuable data for differential diagnosis. MRS and DWI findings provide additional clues on the nature of the lesion.

Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study.

BACKGROUND: In addition to the negative effect on fertility, polycystic ovary syndrome (PCOS) has been associated with cardiac pathology. Brain natriuretic peptide (BNP) is a possible marker for cardiac risk, therefore we investigated whether N-terminal pro-B-type BNP (NT-proBNP) increases in women with PCOS compared with healthy women of comparable age and body mass index. METHODS: Thirty women with PCOS and 30 healthy women not suffering from overt cardiac disease were involved in the study. Fasting insulin and serum NT-proBNP levels were measured, and M-Mode echocardiography was performed. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA-IR). RESULTS: PCOS subjects had higher NT-proBNP levels than the control subjects (P < 0.001). Abnormal echocardiography indices were detected in 14 of the PCOS subjects (but none of the controls), including valvular heart disease in nine, diastolic dysfunction in two, right ventricular enlargement in one, right atrial enlargement in one and pulmonary hypertension in one. PCOS subjects (n = 30) showed an increased left ventricular mass (LVM) (P < 0.001) and left ventricular posterior wall thickness (LVPWT) (P = 0.006). In addition, NT-proBNP concentration was positively correlated with LVM (r = 0.587, P = 0.001) and negatively correlated with sex-hormone-binding globulin (r = -0.528, P = 0.003). There was a positive correlation between LVM and HOMA-IR (r = 0.295, P = 0.03) while LVPWT was positively correlated with fasting insulin and HOMA-IR (r = 0.335, P = 0.031 and r = 0.346, P = 0.045, respectively) in PCOS subjects (n = 30). CONCLUSION: The present study demonstrated that the level of NT-proBNP was increased in PCOS subjects with asymptomatic heart disease.

Diffusion-weighted imaging evaluation of subtle cerebral microstructural changes in intrauterine fetal hydrocephalus.

OBJECTIVE: Hydrocephalus is an important etiological factor in neurological decline. With the advent of fetal ultrasound, fetal hydrocephalus is now more frequently detected than in the past. Ultrasonography (USG) provides information on general morphology, but microstructural changes that may play a prognostic role are beyond the resolution of that technique. These changes may theoretically be revealed by diffusion-weighted magnetic resonance imaging (DW-MRI). In this study, our preliminary findings of DW-MRI on the hydrocephalic fetuses are presented. MATERIALS AND METHODS: Twelve fetuses with fetal USG diagnosis of hydrocephalus were investigated using a 1.5-T MR scanner. In addition to conventional techniques, DWI was performed. It was obtained using a single-shot echo-planar imaging sequence (TR/TE: 4393/81 ms; slice thickness: 5 mm; interslice gap: 1 mm; FOV: 230 mm; matrix size: 128x256; b values: 0 and 1000 s/mm2). Apparent diffusion coefficient (ADC) values were measured in the white matter of the periventricular frontal and occipital lobes, basal ganglia, thalamus, centrum semiovale and cerebrospinal fluid in the lateral ventricle. These values were compared with the normal prenatal ADC values from a radiological study published in the literature. RESULTS: All fetuses had moderate or severe bilateral supratentorial ventricular dilatation that was compatible with hydrocephalus. On conventional T1- and T2-weighted imaging, cerebral parenchyma had normal signal pattern and ADC values were significantly lower than those reported for fetuses with normal brain. These values were lower in hydrocephalic fetuses with statistical significance (P<.05-.01). CONCLUSION: DWI is a sensitive technique to investigate cerebral microstructure. The reduction in cerebral blood flow and alterations in cerebral energy metabolism in cases with hydrocephalus have been shown before. Changes in cerebral blood flow and energy metabolism, as a consequence of cerebral compression, may occur in hydrocephalus. Elevated ventricular pressure may cause cerebral ischemia. The anaerobic glycolysis seen in the hydrocephalic brain tissue by increasing the lactate concentration and intracellular fluid flux may be the reason for the reduced ADC values in hydrocephalic fetuses. However, long-term prospective trials on the correlation of ADC values and neurological outcome are necessary to exploit the full benefit of that novel technique.

Protective role of melatonin in pinealectomized rat brains: in vivo magnetic resonance spectroscopic analysis.

The goal of this study was to investigate the effect of melatonin on basic cerebral metabolites in pinealectomized (Px) rat brains. Twenty-one rats were randomly divided into three groups with seven rats per group. The study groups included sham-operated rats, Px rats and Px rats treated with melatonin. Melatonin administration began at 60 days following pinealectomy and continued for 21 days. At the end of the study, in vivo single voxel magnetic resonance spectroscopy was performed on whole brains to determine choline (Cho), creatine and N-acetyl aspartate (NAA) concentrations. Px rats had significantly lower NAA levels (P<0.05), and significantly higher Cho levels (P<0.05) when compared with sham-operated rats. Administration of melatonin had normalized NAA and Cho levels in Px rats. We propose that pinealectomy causes significant changes in cerebral metabolites which are compatible with neural loss. Melatonin administration prevents the disruptive effects of pinealectomy on brain tissue.

Influence of misoprostol (PGE1) on amniotic fluid and maternal serum adrenomedullin levels.

OBJECTIVE: The purpose of this study was to determine the levels of adrenomedullin (AdM) in amniotic fluid (AF) and maternal serum of misoprostol (PGE1)-induced pregnant women. MATERIALS AND METHODS: A total of 40 women were included in the study: 20 were in active labor and were delivered vaginally and a further 20 were not in labor and misoprostol induction was performed. Women who were undergoing labor induction received 50 microg of misoprostol, which was placed in the posterior fornix of the vagina every 4 hrs until the onset of labor. In each patient, maternal plasma and AF samples were collected. Samples of AF were collected by transvaginal route at the time of rupture of the membranes. The labor was at the same stage in both the groups during the sample collection. In all pregnant subjects, maternal blood samples were drawn from the cubital vein at the time of AF sampling. Amniotic fluid and serum AdM concentration was measured by using reverse-phase high-performance liquid chromatography. RESULTS: Misoprostol-induced pregnant women showed significantly higher AdM concentrations than control pregnant women in AF (79.48 +/- 6.14 pmol/ml versus 21.28 +/- 0.90 pmol/ml, P = 0.000) and maternal serum (88.20 +/- 4.34 pmol/ml versus 29.78 +/- 4.51 pmol/ml, P = 0.000). There was no significant difference between maternal serum and AF-AdM concentrations in misoprostol and control subjects. CONCLUSION: Increased serum and AF-AdM concentrations may be necessary to initiate cervical ripening in misoprostol-induced pregnant women.

Effects of resveratrol, raloxifene, tibolone and conjugated equine estrogen on vaginal squamous cell maturation of ovariectomized rats.

OBJECTIVE: The effects of estrogen replacement therapy, selective estrogen receptor modulators, or tibolone on vaginal squamous cell maturation in postmenopausal women are not well established. Resveratrol (3,5,4'-trans-trihydroxystilbene) has been shown to bind the estrogen receptor in rat uteri. The aim of this study was to cytologically evaluate vaginal smears from ovariectomized rats treated with resveratrol, raloxifene, tibolone and conjugated equine estrogen, and to compare each drug with regard to vaginal epithelial maturation. MATERIAL AND METHODS: Forty-two bilaterally ovariectomized Wistar albino rats were equally randomized into 6 groups: (1) control sham-operated rats; (2) ovariectomized rats administered 0.1% ethanol; (3) ovariectomized rats administered resveratrol at a dose of 5 mg/kg/day p.o.; (4) ovariectomized rats administered conjugated equine estrogen (CEE) at a dose of 0.1 mg/kg/day p.o.; (5) ovariectomized rats administered tibolone at a dose of 0.25 mg/kg/day p.o., and (6) ovariectomized rats administered raloxifen at a dose of 1 mg/kg/day p.o. Administration of drugs started 5 days after bilateral ovariectomy and continued for 35 days. After 35 days of treatment a vaginal smear was obtained from each rat. Smears were stained with the usual Papanicolaou method, and observed with a light microscope by an experienced cytopathologist. Cytological grading was made according to the extent of parabasal, intermediate, superficial and anuclear squamous cells. RESULTS: Ovariectomized rats had lower scores for superficial and anuclear cells when compared to sham-operated rats (p < 0.05). The CEE group had higher scores for superficial and anuclear cells than those of the ovariectomized, raloxifene and tibolone groups (p < 0.05). The resveratrol-treated rats had higher scores for superficial cells but lower scores for parabasal cells than ovariectomized rats (p < 0.05). The raloxifene and tibolone groups had the same scores for intermediate, superficial and anuclear cells but lower scores for parabasal cells compared to ovariectomized rats. CONCLUSION: The results of our study suggest that resveratrol offsets the reduction in vaginal stratification generally observed after oophorectomy.

Clip Turcica: a new apparatus for experimental ovarian ischemia and reperfusion model in rats.

Clip Turcica is a unique, malleable, aluminum apparatus that facilitates holding and release of the adnexa during a period of experimental ovarian ischemia and reperfusion, without anesthesia and laparotomy. The simple opening and closing mechanism of the Clip Turcica allows easier, quicker, and safer application compared with previous methods.

Synchronous endometrial and cervical tumors in a 26-year-old nullipara: diagnostic modalities updated.

Proton magnetic resonance spectroscopy (MRS), performed on conventional magnetic resonance imaging (MRI) scanners, provides useful information at the biochemical level. MRS has been used to measure tissue concentrations of proton-containing compounds such as organic and amino acids, and sugars in living tissues. We have used MRS in a 26-year-old female with suspected cervical and endometrial carcinomas. With the use of the above mentioned technique, biochemical differences in the endometrium and the cervix tissues were detected. The presented case is the first virgin patient in the relevant literature in whom endometrial and cervical carcinoma was detected. Choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lipid and lactate region of the MRS spectrum suggested that the technique could be used as an indicator of metabolic alterations in the cervical and endometrial tumor cells.