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In Young Kim

Publications and source records attributed to In Young Kim.

At least 37 records · Page 2Linked to original sources

Comparison of anti-androgenic activity of flutamide, vinclozolin, procymidone, linuron, and p, p'-DDE in rodent 10-day Hershberger assay.

The rodent Hershberger assay proposed by the Organization for Economic Co-operation and Development (OECD) is in the process of the validating a test method to detecting the androgenic or anti-androgenic compounds. The aim of this study was to compare the anti-androgenic properties of flutamide, vinclozolin, procymidone, linuron, and p,p'-DDE in a 10-day Hershberger assay. In the present study, we used immature Sprague-Dawley male rats castrated at 6 weeks of age. Testosterone propionate (TP) was subcutaneously injected for 10 consecutive days at doses of 0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg per day. To compare the anti-androgenic activity of test compounds, flutamide (1, 5, 10, or 20 mg/kg per day), a pure androgen antagonist was used as a positive control, and administered by oral gavage after TP (0.4 mg/kg per day) treatment. In addition, vinclozolin (25, 50, or 100 mg/kg per day), procymidone (25, 50, or 100 mg/kg per day), linuron (25, 50, or 100 mg/kg per day), and p,p '-DDE (25, 50, or 100 mg/kg per day) were also administered by oral gavage after TP (0.4 mg/kg per day) treatment. As expected, TP dose-dependently increased accessory sex organ weights, and statistically significant effects were observed at doses of 0.1 (only seminal vesicles) or 0.2mg/kg per day and above. Serum testosterone levels increased significantly at 0.4 mg/kg per day and above, while serum LH levels were decreased in a dose-dependent manner. Flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1mg/kg per day and above, and Cowper's glands and glans penis at 5mg/kg per day and above. In contrast to accessory sex organ weights, flutamide did not affect the serum testosterone levels compared to the control at any concentration, but serum LH levels were significantly increased at doses of 10 and 20 mg/kg per day. Similar to flutamide, vinclozolin caused a statistically significant decrease in the weights of seminal vesicles (to 65 and 40% of the control), ventral prostate (to 66 and 51% of the control), LABC (to 81 and 66% of the control), and Cowper's glands (to 81 and 65% of the control) at 50 and 100 mg/kg per day, respectively. Glans penis weight was also significantly reduced (to 79% of the control), but only at 100 mg/kg per day. The most pronounced effects were observed in the procymidone treatment groups. Procymidone significantly inhibited TP-induced re-growth of accessory sex organs at 25mg/kg per day and above, whereas glans penis weight significantly decreased (to 69% of the control), but only at 100 mg/kg per day. Linuron also inhibited TP-induced re-growth of the seminal vesicles (to 72 and 53% of the control), ventral prostate (to 75 and 62% of the control), Cowper's glands (to 74 and 61% of the control) at 50 and 100 mg/kg per day, respectively. LABC (to 65% of the control) and glans penis (to 80% of the control) weights were significantly reduced, but only at 100 mg/kg per day. In case of p,p'-DDE, seminal vesicle weights were significantly decreased at 50 (to 66% of the control) and 100 mg/kg per day (to 58% of the control). In addition, ventral prostate (to 79% of the control), LABC (to 75% of the control), and Cowper's gland (to 82% of the control) weights were reduced, but only at 100 mg/kg per day. On the contrary, no statistically significant differences in serum testosterone or LH levels were observed versus the control. p,p'-DDE significantly increased liver weight in a dose-dependent manner, without affecting on body weights. Our results indicate that procymidone may act as a stronger androgen receptor (AR) antagonist than vinclozolin, linuron, or p,p'-DDE. We conclude that the 10-day Hershberger assay is a sensitive method for detecting potential anti-androgenic compounds.

Administration, Oral↗

Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia.

Changes to the hippocampal structure have been reported as consistent structural abnormalities in schizophrenic patients and have been related to the learning and memory deficits in such patients. Although many magnetic resonance (MR) imaging studies have focused on the hippocampal volume, local structural changes were difficult to discriminate from normal neuroanatomical variations. 3D shape deformation analysis of the brain structure may reflect localized schizophrenic abnormalities. A deformable model, evolved from the ellipsoid to hippocampal surface, with 2562 vertexes, was developed to analyze the left and right hippocampus shapes in 22 schizophrenic patients and 22 healthy age and gender matched controls. One of the most critical issues in the shape analysis is the determination of homologous points between two objects. To determine more accurate corresponding points, an alignment procedure, consisting of coarse and fine steps, following a deformation process, was applied. The performance of the alignment process was tested using artificial data, to get the alignment error to within 3 degrees for each angle. A volume analysis indicated the hippocampal volume to be bilaterally reduced in schizophrenic patients compared to the normal controls, with a shape analysis showing a deformity pattern of the hippocampal surface. Bilateral inward deformities in the anterior and posterior hippocampus and a unilateral outward deformity in the right anterior hippocampus were observed, respectively.

Adult↗

Phthalates inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer cells.

Environmental estrogens represent a class of compounds that can mimic the function or activity of the endogenous estrogen 17 -estradiol (E2). Phthalates including butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP) are used as plasticizers, and also widely used in food wraps and cosmetic formulations. Phthalates have been shown to mimic estrogen and are capable of binding to the estrogen receptor (ER). It has been demonstrated that estrogen promotes drug resistance to tamoxifen (TAM) in breast cancer. In order to further evaluate the potential role of the phthalates as environmental estrogens, the effect of phthalates was investigated on TAM-induced apoptosis in MCF-7 human breast cancer cells. Our results show that phthalates, BBP (100 M), DBP (10 M), and DEHP (10 M), significantly increased cell proliferation in MCF-7, but not in MDA-MB-231 cells. In addition, BBP, DBP, and DEHP mimicked estrogen in the inhibition of TAM-induced apoptosis in MCF-7 cells. Our data suggest that the inhibitory effect of phthalates on TAM-induced apoptosis involves an increase in intracellular Bcl-2 to Bax ratio. Given that the phthalates are widely used in cosmetics mainly for women, our findings that revealed the promoting effect of BBP, DBP, and DEHP on chemotherapeutic drug resistance to TAM in breast cancer may be of biological relevance.

Antineoplastic Agents, Hormonal↗

Neonatal exposure to di(n-butyl) phthalate (DBP) alters male reproductive-tract development.

The purpose of this study was to evaluate male reproductive-organ development in early postnatal male rats following neonatal exposure to di(n-butyl) phthalate (DBP) and identify a mechanism of action. Neonatal male rats were injected subcutaneously from d 5 to 14 after birth with corn oil (control) and DBP (5, 10, or 20 mg/animal). Animals were killed at postnatal day (PND) 31 and PND 42, respectively, and testes, epididymis, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscles (LABC), and Cowper's glands were weighed. In addition, the expressions of androgen receptor (AR), estrogen receptors (ERs), and steroidogenic factor-1 (SF-1) were also examined in the testes. Total body weights gains were significantly reduced at PND 29-31, but gradually recovered on PND 42. However, DBP (20 mg/animal) significantly reduced the weights of testes and accessory sex organs (seminal vesicles, LABC, and Cowper's glands), but not of the epididymis. These adverse effects persisted through puberty at PND 42. Serum testosterone levels did not show any significant changes in the control and DBP treatment groups. Histomorphological examination showed mild diffuse Leydig-cell hyperplasia in the interstitium of severely affected tubules on PND 31. Only a few multinuclear germ cells were observed. DBP (20 mg/animal) significantly decreased the expression of AR, whereas ER expression and SF-1 expression were increased in a dose-dependent manner on PND 31 in the rat testes. On PND 42, DBP (20 mg/animal) significantly inhibited ER expression in the testes, but not AR, ER, and SF-1. These results demonstrate that neonatal exposure to DBP produces permanent changes in the endocrine system and leads to abnormal male reproductive-tract development until puberty. Thus our data suggest that DBP is likely to exert its antiandrogenic actions through disruption of AR or ER expression during the early neonatal stage.

Animals↗

Neurofeedback training with virtual reality for inattention and impulsiveness.

In this research, the effectiveness of neurofeedback, along with virtual reality (VR), in reducing the level of inattention and impulsiveness was investigated. Twenty-eight male participants, aged 14-18, with social problems, took part in this study. They were separated into three groups: a control group, a VR group, and a non-VR group. The VR and non-VR groups underwent eight sessions of neurofeedback training over 2 weeks, while the control group just waited during the same period. The VR group used a head-mounted display (HMD) and a head tracker, which let them look around the virtual world. Conversely, the non-VR group used only a computer monitor with a fixed viewpoint. All participants performed a continuous performance task (CPT) before and after the complete training session. The results showed that both the VR and non-VR groups achieved better scores in the CPT after the training session, while the control group showed no significant difference. Compared with the other groups, the VR group presented a tendency to get better results, suggesting that immersive VR is applicable to neurofeedback for the rehabilitation of inattention and impulsiveness.

Adolescent↗

A virtual reality assessment and training system for unilateral neglect.

Patients with unilateral neglect have problems reporting, responding, or orienting to novel or meaningful stimuli that is presented to the side opposite to that of a brain lesion. This creates a serous problem in regards to daily living activities. However, the established methods for assessing and training of unilateral neglect patients have several deficits. Recently, virtual reality (VR) technologies have been used as an assessment and treatment tool for rehabilitation. Hence, this study designed a VR system to assess and train unilateral neglect patients. In addition, the suitability and feasibility of our VR system for unilateral neglect patients was verified.

Activities of Daily Living↗

Analysis of the hemispheric asymmetry using fractal dimension of a skeletonized cerebral surface.

We investigated hemispheric asymmetry using the fractal dimension (FD) of the skeletonized cerebral surface. Sixty-two T1-weighted magnetic resonance imaging volumes from normal Korean adults were used. The skeletonization of binary volume data, which corresponded to the union of the gray matter and cerebrospinal flow classified by fuzzy clustering, was performed slice by slice in the sagittal direction, and then skeletonized slices were integrated into the three-dimensional (3-D) hemisphere. Finally, the FD of the 3-D skeletonized cerebral surface was calculated using the box-counting method. We measured the FD of the skeletonized cerebral surface and the volumes of intracranial gray matter and white matter for the whole hemispheres and obtained the hemispheric asymmetries of each measurement. The FD, the gray matter, and the white matter volumes for the whole hemispheres decreased in the old group. The asymmetry of the FD revealed a significant right-greater-than-left asymmetry showed rightward, but did not change according to age and gender. None of the intracranial gray matter or white matter volumes showed any significant asymmetric changes. It could be said that the FD of the skeletonized cerebral surface is a novel measure of cerebral asymmetry.

Adolescent↗

Assessing estrogenic activity of pyrethroid insecticides using in vitro combination assays.

Pyrethroid insecticides are among the most commonly used classes of insecticides worldwide, but their endocrine disrupting activities remain unclear. Therefore, in the present study, we examined the estrogenic activities of pyrethroid insecticides in E-screen and competition binding assays. In addition, we measured estrogen receptor (ER) protein and pS2 mRNA levels in human breast cancer cells (MCF-7 BUS) to clarify the mechanism of their estrogenicity. Seven pyrethroid insecticides (bioallethrine, cypermethrin, deltamethrin, fenvalerate, permethrin, sumithrin, and tetramethrin) were tested because of their worldwide usage. In addition, 17beta-estradiol was tested as a positive control. As expected, 17beta-estradiol significantly increased MCF-7 BUS cell proliferation at concentrations of 10(-11) M and above. Of the pyrethroid insecticides tested, only sumithrin increased MCF-7 BUS cell proliferation in a dose-dependent manner; the maximum induction of cell proliferation was observed at a dose of 10(-5) M. In the anti-estrogenic activity test, bioallethrin, fenvalerate, and permethrin significantly inhibited 17beta-estradiol-induced MCF-7 BUS cell proliferation at 10(-6) M, a concentration comparable to the effective dose (10(-9) M) of ICI 182,780, a pure ER antagonist. However, none of the pyrethroid insecticides competitively inhibited the binding of [(3)H]estradiol to rat uterus ERs in competition binding assays. Both 17beta-estradiol (10(-10) M) and sumithrin (10(-5) M) decreased the levels of cytosolic ERalpha and ERbeta protein expression significantly as compared with the vehicle control. In addition, 17beta-estradiol (10(-10) M) increased pS2 mRNA expression markedly, and sumithrin significantly increased pS2 mRNA levels in a dose-dependent manner. The other six compounds tested in the present study did not affect ER protein levels or pS2 mRNA levels. These results suggest that certain pyrethroid insecticides may be considered to be estrogen-like chemicals that act through pathways other than direct ER binding, and may function as endocrine modulators in both wildlife and humans.

Animals↗

Morphometric abnormality of the insula in schizophrenia: a comparison with obsessive-compulsive disorder and normal control using MRI.

The insula is increasingly the subject of great interest in psychiatric disorders of neurodevelopmental origin because of its anatomical location, wide interconnectivity, and variety of functions. This study explores the possible morphometric change of the insula in schizophrenia and obsessive-compulsive disorder (OCD), and its potential relationship to clinical symptoms. The insula was traced on all coronal slices of magnetic resonance images of three age- and sex-matched diagnostic groups, which consisted of 21 patients with schizophrenia, 21 patients with OCD and 21 normal volunteers. The volumetric measures of the insula were compared among the three groups, and their relationships to the symptom severity were investigated. Volumetric reduction of the left insula was observed in the schizophrenia group, but not in the OCD group. These results confirm the involvement of deficient insular function in the pathophysiology of schizophrenia.

Adult↗

Modified magnetic resonance image based parcellation method for cerebral cortex using successive fuzzy clustering and boundary detection.

Development of the accurate and reproducible parcellation of the human brain can be used to resolve the complex structure-functional relationships in the brain. We propose a modified parcellation method that provides the reliable and reproducible regions of interest using successive fuzzy c-means (sFCM) and boundary-detection algorithm. This method displays simultaneously both original brain image for identifying the sulcal landmarks and its tissue-classified image for referring to patterns of sulci. The whole cerebral region is extracted by the semiautomated region growing method and then classified to gray matter, white matter, and cerebrospinal fluid by sFCM. Referred to the other previous researches, the volume ratio of gray matter to white matter was shown to find that the efficiency of classification was improved (conventional FCM: 0.80 +/- 0.12 vs. sFCM: 1.57 +/- 0.18). Inter-rater reliability, estimated by the regression analysis, demonstrated that the proposed method was more reliable and reproducible than conventional methods [ANALYZE: correlation coefficient (CC)=0.341, Sig.=0.335 vs. proposed method: CC=0.816, Sig.=0.004]. The volume ratio of the whole cerebrum to the parceled object can be used to investigate structural abnormalities for the pathological detection of the various mental diseases such as schizophrenia, obsessive-compulsive disorder.

Algorithms↗

No androgenic/anti-androgenic effects of bisphenol-A in Hershberger assay using immature castrated rats.

Several studies have demonstrated that bisphenol A (BPA) exhibited weak estrogenic activity in the 3-day uterotrophic assay using ovariectomized (OVX) and immature rats (Toxicol. Lett. 115 (2000) 231; Regul. Toxicol. Pharmacol. 32 (2000) 118; J. Toxicol. Sci. 26 (2001) 111) and BPA also possessed anti-androgenic activity in in vitro yeast based assays (J. Endocrinol. 158 (1998) 327). To investigate anti-androgenic effects of BPA. a rodent Hershberger assay was carried out using immature Sprague-Dawley male rats. An androgen agonist, testosterone (0.4 mg/kg per day), was administered for 7 consecutive days by subcutaneous (s.c.) injection as a positive control. Additionally, a pure androgen antagonist, flutamide (1, 5. 10 mg/kg per day. oral) was co-administered with testosterone (0.4 mg/kg per day s.c.). BPA was also administered orally with or without testosterone (0.4 mg/kg per day, s.c.) for 7 consecutive days. In the testosterone treated groups, glans penis, seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles (LABC) weights were significantly increased compared with control. However. flulamide dose-dependently inhibited the testosterone-induced re-growth of seminal vesicles, ventral prostate, and LABC, with a significant decrease at flutamide 1.0 mg/kg and above (P<0.05). Serum LH levels were also significantly increased (5 mg/kg and above, P<0.05), but no changes in serum testosterone levels. In contrast, BPA had no effects on the re-growth of seminal vesicles, ventral prostate and LABC induced by testosterone, and no significant differences were observed in serum LH and testosterone levels. In summary, the Hershberger assay could be a sensitive method for detecting androgenic or anti-androgenic chemicals, but BPA did not exhibit any androgenic or anti-androgenic activities in Hershberger assay.

Androgen Antagonists↗

Detrended fluctuation analysis of EEG in sleep apnea using MIT/BIH polysomnography data.

A number of natural time series including electroencephalogram (EEG) show highly non-stationary characteristics in their behavior. We analyzed the EEG in sleep apnea that typically exhibits non-stationarity and long-range correlations by calculating its scaling exponents. Scaling exponents of the EEG dynamics are obtained by analyzing its fluctuation with detrended fluctuation analysis (DFA), which is suitable for non-stationary time series. We found the mean scaling exponents of EEG is discriminated according to Non-REM, REM (Rapid Eye Movement) and waken stage, and gradually increased from stage 1 to stage 2, 3 and 4.

Cerebral Cortex↗

Effects of flutamide on puberty in male rats: an evaluation of the protocol for the assessment of pubertal development and thyroid function.

To establish a test protocol for the rodent 20-d thyroid/pubertal assay, flutamide, a non-steroidal androgen antagonist, was administered to intact male Sprague-Dawley rats from postnatal d 33 for 20 d, and several reproductive endpoints were examined to assess the sensitivity of a number of parameters with respect to the detection of endocrine-related effects. Immature male rats were divided into 4 groups and given flutamide once daily by oral gavage at doses of 0, 1, 5, or 25 mg/kg/d. Prepuce separation was significantly delayed in flutamide-treated rats (5 and 25 mg/kg/d). One day after the last dose, the rats were sacrificed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani plus bulbocavernosus muscles, Cowper's glands, and glans penis. The weight of adrenal glands decreased at 25 mg/kg/d, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone were significantly increased in the flutamide-treated groups (5 and 25 mg/ kg/d) and serum levels of estradiol were also increased (25 mg/kg/d). No differences were observed in the serum thyroxine levels. These results indicate that flutamide delays puberty in the male rat, and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. Thus, this assay might be used as an alternative for screening antiandrogenic activities of chemicals.

Androgen Antagonists↗

The effect of virtual reality cognitive training for attention enhancement.

Our main goal in this research was to validate the possibility of virtual reality (VR) for attention enhancement in cognitive training program. Then, we developed some cognitive training tasks using VR technology. Thirty subjects who had little behavioral problems and social problems were randomly assigned into three groups: VR group, non-VR group, and control group. Only the VR group used the head-mounted display (HMD) and position sensor. While the VR group and non-VR group performed cognitive training, the control group received no special treatment. All participants took their eight session tasks over 2 weeks. Participants executed a continuous performance task (CPT) before and after training sessions. We found that immersive VR with cognitive training is effective for attention enhancement. Also, we confirmed that our cognitive training can improve the attention span of children and adolescents with behavioral problems and help them learn to focus on some tasks.

Adolescent↗

Evaluation of the 20-day pubertal female assay in Sprague-Dawley rats treated with DES, tamoxifen, testosterone, and flutamide.

The Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC) has recommended the rodent pubertal female assay as a Tier I test to detect potential endocrine disrupters (EDs). This assay is designed to screen estrogenic activity in immature rats exposed to chemicals during sexual maturation. The aim of this study was to evaluate whether this assay can detect the EDs with effects brought about through various mechanisms. Immature Sprague-Dawley female rats (21 days of age) were dosed daily for 20 days by oral gavage (DES, tamoxifen, and flutamide) or sc injection (testosterone). The mean age at vaginal opening (VO) was 32.3 +/- 0.5 days in control rats. Although VO was unaffected by DES at doses of 0.2 and 1.0 microg/kg, a high dose of DES (5.0 microg/kg) significantly advanced the age at VO to 24 days. Both tamoxifen (50 and 200 microg/kg) and flutamide (25 mg/kg) also significantly accelerated VO to 27.8 +/- 0.5, 25.1 +/- 0.1, and 26.1 +/- 0.1, respectively. However, testosterone dose-dependently delayed VO (exposure to 1.0 mg/kg extended VO to 37.3 +/- 0.8 days, and VO did not occur in 2 of 10 animals by the time of necropsy at 41 days of age). Estrous cyclicity was monitored in rats from VO to necropsy. Irregular cycles were observed in the groups treated with DES (5.0 microg/kg), tamoxifen (200 microg/kg), testosterone (1.0 mg/kg), and flutamide (25 mg/kg). High dose of DES showed a persistent estrus state throughout the entire observation period. In addition, the number of days in diestrus was increased by tamoxifen (200 microg/kg) and flutamide (25 mg/kg) treatments. Significant decreases in ovarian weight were observed in 5.0 microg/kg DES (64% of control), 25 mg/kg flutamide (76% of control), and 200 microg/kg tamoxifen (47% of control). Testosterone also significantly decreased the ovarian weights in all treatment groups. Uterine weights were also decreased significantly at high doses of tamoxifen (200 microg/kg, 39% of control) or testosterone (1.0 mg/kg, 47% of control). In hormone analysis, tamoxifen significantly increased serum E(2) levels at 50 microg/kg. The mean serum levels of TSH were significantly increased in tamoxifen (10 and 50 microg/kg), testosterone (0.2 mg/kg), and flutamide (1.0 and 25 mg/kg) treatment groups compared with the control. However, serum T(4) levels were significantly reduced by testosterone. Furthermore, serum T(3) levels were significantly increased in DES, tamoxifen (10 and 50 microg/kg), testosterone (1.0 mg/kg), and flutamide (1.0 and 5 mg/kg). Our data demonstrate that the rodent pubertal female assay is useful for identifying potential EDs having not only estrogenic/antiestrogenic but also androgenic/antiandrogenic activities. However, further validation study is necessary to identify chemicals that operate through other action mechanisms, including steroid biosynthesis inhibitors and thyroid inhibitors. Moreover, additional data on other compounds with weak endocrine disrupting activity will be required to further characterize the sensitivity of the female pubertal assay.

Administration, Oral↗

Simultaneous occurrence of subarachnoid hemorrhage due to ruptured aneurysm and remote hypertensive intracerebral hemorrhage: case report.

Simultaneous occurrence of aneurysmal subarachnoid hemorrhage (SAH) and hypertensive intracerebral hemorrhage (ICH) is very rare and only two cases have been previously reported in the literatures. We present a case of 68-yr-old man with a history of untreated hypertension, who suffered from sudden onset of headache followed by right hemiparesis. Computed tomographic (CT) scan revealed SAH in the basal cistern and remote ICH at the left putamen. Cerebral angiography showed a saccular aneurysm at the anterior communicating artery. No other vascular anomaly could be found at left putaminal area. Nine days after the ictal attack of SAH, the neck of aneurysm was clipped via the left frontotemporal craniotomy. Because of the ICH at the left frontal lobe and intraventricular hematoma on postoperative CT, we performed hematoma removal and external ventricular drainage 3 hours after the first operation. Postoperative neurological status had been improved to be drowsy and he was discharged in a severely disabled state 4 weeks after surgery. We suggest that the rupture of aneurysm possibly caused a rapid increase in blood pressure and subsequently resulted in hypertensive ICH.

Aged↗

Fractal dimension of cerebral cortical surface in schizophrenia and obsessive-compulsive disorder.

Schizophrenia and obsessive-compulsive disorder (OCD) are assumed to be neurodevelopmental disorders. To examine the cortical patterns in the two disorders, three-dimensional fractal dimension (FD) of skeletonized cerebral cortical surface was estimated from magnetic resonance (MR) images of 50 patients with schizophrenia, 45 patients with OCD and 26 healthy normal controls. The schizophrenic group had a significantly smaller mean FD than OCD group, and the OCD group than normal controls. The FD revealed a significant interaction effect of group-by-hemisphere, and the FD asymmetry index distinguished the schizophrenic group from normal controls. In logistic regression models, the FD and CSF volume correctly classified 95.6% of the schizophrenics from the controls and 88.0% of the patients with OCD from the controls. In the control and schizophrenic groups, the FD was not associated with any of tissue volume measures. In the OCD group, however, the FD was significantly correlated with gray matter tissue volume and intracranial volume (ICV). The results of the present study suggest that three-dimensional FD of cortical surface may be a sensitive indicator for investigation of the structural brain abnormalities in mental disorders, especially those developmentally disturbed. Further studies to explore regional FD changes in mental disorders and clinical implications of the FD including diagnostic value should be performed in the future.

Adult↗

Comparative estrogenic effects of p-nonylphenol by 3-day uterotrophic assay and female pubertal onset assay.

Nonylphenol (NP) is widely used as a component of detergents, paints, pesticides, and many other formulated products. Several studies have demonstrated that NP is estrogenic in fish, avian, and mammalian cells. NP also competitively inhibits the binding of 17 beta-estradiol (E2) to the estrogen receptor (ER). However, there are relatively few in vivo data related to this issue in mammals. The aim of this study was to investigate the estrogenic activity of NP in animal models. We performed a 3-day uterotrophic assay using immature female rats for comparison with other endpoints of Tier I screening including vaginal opening (VO) in prepubertal intact female rats. For the uterotrophic assay, diethylstilbestrol (DES) (0.2 and 1.0 microg/kg) and p-NP (10, 25, 50, 100, and 200 mg/kg) were administered subcutaneously to immature Sprague-Dawley female rats for 3 consecutive days (postnatal days (PND) 20, 21, and 22). For the female pubertal onset assay, DES (0.2, 1.0, and 5.0 microg/kg) and p-NP (10, 50, and 100 mg/kg) were administered daily by oral gavage from 21 days of age for 20 days. In the uterotrophic assay, statistically significant increases in uterine wet weight were observed at doses of 100 and 200 mg/kg p-NP. DES (0.2 and 1.0 microg/kg) also significantly increased uterine weight compared to the vehicle control. In the female pubertal onset assay, the age of VO was advanced following oral exposure to DES (1.0 and 5.0 microg/kg) and p-NP (50 and 100 mg/kg). Estrous cyclicity was monitored in prepubertal rats from the day of VO to the day of necropsy. Irregular estrous cycles were observed in the groups treated with DES (5.0 microg/kg) and p-NP (50 and 100 mg/kg). High-dose DES (5.0 microg/kg) produced a persistent estrus state, whereas p-NP (50 and 100 mg/kg) increased the number of days in diestrus. Serum thyroxine (T(4)) concentrations were decreased in a dose-dependent manner by DES and p-NP treatment. A significant decrease in serum T(4) level was observed at high-dose DES (5.0 microg/kg) and p-NP (100 mg/kg). Serum TSH level was significantly increased by DES (5.0 microg/kg) treatment. Statistically significant decreases in ovarian weight were observed in female rats treated with DES (5.0 microg/kg) and p-NP (100 mg/kg). Our data demonstrate that p-NP can accelerate the onset of puberty and alter estrous cyclicity in prepubertal female rats at oral doses lower than the subcutaneous doses typically used in the uterotrophic assay. We therefore suggest that the female pubertal onset assay may be used as a sensitive testing method to detect environmental agents with weak estrogenic activity, but requires further research.

Administration, Oral↗