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.

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.

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.

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.

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.

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.

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.

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 effect of melatonin against oxidative stress on adhesion formation in the rat cecum and uterine horn model.

This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) and the effect of melatonin on these metabolites in a postoperative intraperitoneal adhesion formation model in rats. Thirty adult female Wistar albino rats were subjected to standardized lesions by cecal and uterine horn abrasion and were randomly divided into three groups. Control rats were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin before closure and for 10 consecutive days intraperitoneally after surgery. Rats in the sham operation group underwent a surgical procedure similar to the other groups however the peritoneal abrasion was not performed. On postoperative day 10 relaparatomy was performed. After the assessment of the adhesions, the rats in each group were sacrificed and peritoneal tissues were harvested to determine the tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the melatonin group were significantly lower than that of control and sham group (p<0.01 and p<0.02, respectively). Tissue levels of MDA and NO were significantly lower in the melatonin treated rats when compared with control and sham groups. The levels of GSH in the melatonin treated rats were significantly higher than those of control and sham groups (p<0.01). The results demonstrate that in this experimental model, intraperitoneal administration of melatonin decreases the extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH levels.

Magnetic resonance spectroscopic comparison of the effects of resveratrol (3,4',5-trihydroxy stilbene) to conjugated equine estrogen, tibolone and raloxifene on ovariectomized rat brains.

OBJECTIVE: To investigate the effects of resveratrol on basic cerebral metabolites of in the brains of ovariectomized rats. MATERIALS AND METHODS: Twenty-four bilaterally ovariectomized rats were randomly assigned into six groups with four rats in each group. The groups consisted of sham-operated (control), ovariectomized, resveratrol, conjugated equine estrogen (CEE), tibolone and raloxifene treated rats. Drug administration started at the 5th day following ovariectomy and continued for 35 days. At the end of the entire course, in vivo single voxel magnetic resonance spectroscopy was performed on whole brains to determine choline, creatine and N-acetyl aspartate (NAA) concentrations. RESULTS: Compared to sham-operated group, ovariectomized group had significantly lower NAA (P<0.008) but significantly higher choline levels (P<0.031). Administration of CEE and resveratrol resulted in NAA levels that were similar to those in the sham-operated group, showing that the NAA decrease due to ovariectomy was prevented. Treatment with tibolone and raloxifene resulted in a smaller increase in NAA and the effect failed to reach significance. Administration of resveratrol, CEE, tibolone and raloxifene resulted in choline levels similar to those in sham-operated group, showing that the increase in the ovariectomy group was prevented. CONCLUSION: Resveratrol causes levels of cerebral metabolites that is similar to conventional hormone replacement agents. This finding may suggest that neuronal function in the postmenopausal state was preserved. More detailed investigation of this issue should be the task of future research.

Magnetic resonance spectroscopy of premalignant and malignant endometrial disorders: a feasibility of in vivo study.

OBJECTIVE: To assess the potential clinical utility of in vivo proton magnetic resonance spectroscopy (MRS) in patients with various endometrial lesions. METHODS: Twelve patients with untreated uterine bleeding were included in this study. In-vivo proton MRS was performed using a 1.5 T MR scanner. The metabolite levels were classified into three classes in comparison with the noise level by visual examination. All the patients have endometrial biopsy. For each type of lesions, chemical compound were described. RESULTS: Pathological examination resulted in three endometrial cancer, two simple hyperplasias, one complex hyperplasia, two partial hydatiform mole, two proliferative endometrium and two secretory endometrium. In women with endometrial carcinoma, high choline and lipid signals were detected, whereas no creatine and no lactate signals were found. In women with endometrial hyperplasia, choline signal was detectable in all cases but one case showed lactate signal in addition to choline. In women with partial hydatidiform mole, the only detectable signal was choline. Lipid signals were detected in none of the cases with endometrial hyperplasia and partial hidatidiform mole. In women with either secretory or proliferative endometrium, choline and lactate signals were detectable in all cases but one case showed solely choline. Lipid signals were not detected in any of subjects with secretory or proliferative endometrium. CONCLUSION: The observed difference is the presence of lipid signal only in endometrial carcinoma.

Effect of electromagnetic field emitted by cellular phones on fetal heart rate patterns.

The study was planned to determine the effects of electromagnetic fields produced by cellular phones on baseline fetal heart rate, acceleration and deceleration. Forty pregnant women undergoing non-stress test were admitted to the study. Non-stress test was obtained while the subjects were holding the CP on stand by mode and on dialing mode, each for 5 min. Similar recordings were taken while there were no phones around for 10 min. Electromagnetic fields produced by cellular phones do not cause any demonstrable affect in fetal heart rate, acceleration and deceleration.

Cerebrospinal fluid nitric oxide level changes in preeclampsia.

OBJECTIVE: The purpose of this study was to determine the level of nitric oxide (NO) metabolites, nitrite and nitrate in human cerebrospinal fluid (CSF) and serum and to assess whether there is any relationship among CSF, serum nitrate-nitrite levels and preeclampsia. STUDY DESIGN: Twenty-one preeclamptic and 27 healthy pregnant women as control group who underwent cesarean section (C/S) were included in the study. Before administering local anesthetic for spinal anesthesia, 2 ml CSF and 4 ml venous blood sample were taken. CSF and serum total nitrite, direct nitrite and nitrate levels were determined spectrophotometrically. RESULTS: CSF total nitrite, direct nitrite and nitrate levels were significantly different between the two groups (21.00+/-1.68, 8.28+/-0.89 and 12.71+/-1.08 micromol/l, respectively versus 15.53+/-1.49, 5.57+/-0.39 and 9.96+/-1.45 micromol/l, respectively, P<0.05). Significantly higher serum nitrate level was found (31.84+/-2.31 micromol/l) in the control group compared to the preeclamptic group serum nitrate level (25.06+/-2.02 micromol/l). Statistical comparisons were performed by the Mann-Whitney U-test. CONCLUSION: CSF-NO is significantly higher but serum NO is lower in preeclamptic group compared with control group may suggest independent regulation of NO in the two compartments. The determination of CSF-NO metabolites could be useful to clarify whether increased NO production is predominantly associated with poor perfusion of the brain in preeclampsia.

The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary.

OBJECTIVE: This experimental study was designed to determine the changes in tissue levels of malondialdehyde, end-product of lipid peroxidation (MDA), reduced glutathione (GSH) and xanthine oxidase (XO) and the effect of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) on these metabolite levels after adnexal torsion-detorsion model in rats. METHOD: Forty adult female albino rats were divided into five groups: basal control (n = 8), sham operation (n = 8), torsion-detorsion plus saline (n = 8), torsion-detorsion plus CAPE (n = 8). and only torsion (n = 8). Rats in the sham operation group underwent a surgical procedure similar to the other groups but the adnexa was not torsioned. Rats in the torsion group were killed after 360 degrees clockwise adnexal torsion for 3 h and ovaries were harvested. CAPE was injected intraperitoneally 30 min before detorsion in the CAPE/detorsion group and saline was administered in the saline/detorsion group. After 3 h of adnexal detorsion, the rats in both groups were killed and adnexa were surgically removed. RESULTS: MDA levels and XO activities in torsion-detorsion plus saline group increased significantly when compared to basal control, torsion and sham operation groups (P < 0.001). In the CAPE group, MDA levels and XO activities were lower than those of torsion-detorsion plus saline group, and differences between the two groups were statistically significant (P < 0.001). GSH levels in torsion-detorsion plus saline group were decreased significantly when compared to basal control and sham operation groups (P < 0.001). GSH levels in the CAPE group were higher than those of torsion-detorsion plus saline group, and differences between the two groups were statistically significant (P < 0.004). Morphologically, polymorphonuclear leukocytic infiltration and vascular dilatation were obvious in the ischemia-reperfusion damaged ovary, a change partially reversed by CAPE. CONCLUSIONS: These results suggest that administration of CAPE has beneficial effects in the prevention of ischemia-reperfusion injury of the ovaries.

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.

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.

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.

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.

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.

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.