A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice.

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×-13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.

Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine ß-Synthase-Deficient Mice, an Animal Model of Homocystinuria.

Mental retardation is the most common feature among inborn errors of amino acid metabolism. Patients with homocystinuria/homocysteinemia caused by cystathionine ß-synthase (CBS) deficiency suffer from thromboembolism and mental retardation from early ages; therefore, detection by newborn screening is performed. Furthermore, elevated levels of serum homocysteine during pregnancy are associated with the occurrence of neural tube defects (NTDs) in newborns. However, the causes of such central nervous system (CNS) defects are unknown. We found previously impaired learning abilities in Cbs-deficient (Cbs-/-) mice (but not NTD births). Here, we investigated the amino acid profiles of serum and cerebrospinal fluid (CSF) from Cbs-/- mice. Mice deficient in cystathionine γ-lyase (Cth), a downstream enzyme of CBS in transsulfuration, as well as wild-type mice, were analyzed as controls. Cbs-/- and Cth-/- mice were smaller than wild-type mice, and CSF yields in Cbs-/- mice were lower than the others. CSF amino acid levels were generally lower than those in serum, and compared with the dramatic amino acid level alterations in Cbs-/- mouse serum, alterations in CSF were less apparent. However, marked upregulation (versus wild-type) of aspartic acid/asparagine (Asp/Asn), glutamine (Gln), serine (Ser), threonine (Thr), phenylalanine (Phe), tyrosine (Tyr), methionine (Met), total homocysteine, and citrulline, and downregulation of lysine (Lys) were found in Cbs-/- mouse CSF. Because similar regulation of total homocysteine/citrulline/Lys was observed in the CSF of Cth-/- mice, which are free of CNS dysfunction, the reduced CSF volumes and the level changes of other amino acids could be relevant to Cbs-/--specific CNS defects.

Coordinated regulation of the dorsal-ventral and anterior-posterior patterning of Xenopus embryos by the BTB/POZ zinc finger protein Zbtb14.

During early vertebrate embryogenesis, bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-ß (TGF-ß) family of growth factors play a central role in dorsal-ventral (DV) patterning of embryos, while other growth factors such as Wnt and fibroblast growth factor (FGF) family members regulate formation of the anterior-posterior (AP) axis. Although the establishment of body plan is thought to require coordinated formation of the DV and AP axes, the mechanistic details underlying this coordination are not well understood. Here, we show that a Xenopus homologue of zbtb14 plays an essential role in the regulation of both DV and AP patterning during early Xenopus development. We show that overexpression of Zbtb14 promotes neural induction and inhibits epidermal differentiation, thereby regulating DV patterning. In addition, Zbtb14 promotes the formation of posterior neural tissue and suppresses anterior neural development. Consistent with this, knock-down experiments show that Zbtb14 is required for neural development, especially for the formation of posterior neural tissues. Mechanistically, Zbtb14 reduces the levels of phosphorylated Smad1/5/8 to suppress BMP signaling and induces an accumulation of ß-Catenin to promote Wnt signaling. Collectively, these results suggest that Zbtb14 plays a crucial role in the formation of DV and AP axes by regulating both the BMP and Wnt signaling pathways during early Xenopus embryogenesis.

Intramolecular interactions that induce helical rearrangement upon rhodopsin activation: light-induced structural changes in metarhodopsin IIa probed by cysteine S-H stretching vibrations.

Rhodopsin undergoes rearrangements of its transmembrane helices after photon absorption to transfer a light signal to the G-protein transducin. To investigate the mechanism by which rhodopsin adopts the transducin-activating conformation, the local environmental changes in the transmembrane region were probed using the cysteine S-H group, whose stretching frequency is well isolated from the other protein vibrational modes. The S-H stretching modes of cysteine residues introduced into Helix III, which contains several key residues for the helical movements, and of native cysteine residues were measured by Fourier transform infrared spectroscopy. This method was applied to metarhodopsin IIa, a precursor of the transducin-activating state in which the intramolecular interactions are likely to produce a state ready for helical movements. No environmental change was observed near the ionic lock between Arg-135 in Helix III and Glu-247 in Helix VI that maintains the inactive conformation. Rather, the cysteine residues that showed environmental changes were located around the chromophore, Ala-164, His-211, and Phe-261. These findings imply that the hydrogen bond between Helix III and Helix V involving Glu-122 and His-211 and the hydrophobic packing between Helix III and Helix VI involving Gly-121, Leu-125, Phe-261, and Trp-265 are altered before the helical rearrangement leading toward the active conformation.

Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.

Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

Magnetoelectric effect driven by magnetic domain modification in LuFe2O4.

The magnetocapacitance effect was investigated using impedance spectroscopy on single crystals of LuFe(2)O(4). The intrinsic impedance response could be separated from the interfacial response and showed a clear hysteresis loop below T(Ferri)∼240 K under the magnetic field. The neutron diffraction experiment under the magnetic field proves the origin of the dielectric property related to the motion of the nanosized ferromagnetic domain boundary. These results imply that the modification of the microscopic domain structure is responsible for the magnetoelectric effect in LuFe(2)O(4).

[Home care and place of death for elderly people living in the remote islands of Japan. An examination on the presence of inpatient facilities].

OBJECTIVES: The purpose of this study was to clarify the actual status of end-of-life care for elderly people living in the remote islands of Japan, and whether the presence of inpatient facilities was related to the place of death, so as to obtain suggestions for constructing a system of end-of-life care. METHODS: The survey targeted caregivers (85 people) who cared for elderly people (aged 65 and over), who had been legally certified for long-term care, and who had died between April 2009 and July 2011 in five islands of Japan. Islands were selected from a list of remote islands specified in the Remote Islands Development Act and related laws. Using a mixed method embedded design, we conducted semi-structured interviews using a questionnaire that assessed the place and cause of the elderly patient's death, age at death, gender, and whether the patient or family members had requested that the patient be allowed to die at home. RESULTS: The proportion of elderly people who died at home in the group living on remote islands with no inpatient facilities was 39.0% (16 of 41 people), compared with 18.2% (8 of 44 people) living on islands with inpatient facilities. The difference was significant (P=0.029). Among the 24 elderly people who died at home, 6 died of cancer. Terminally ill cancer patients were released to die at home under three conditions: the caregivers could provide sufficient care, the visiting physician was present, and pain control was provided. It was also possible for elderly cancer patients to receive end-of-life care in remote islands that did not have inpatient facilities. In addition, among the elderly people who died at home in the remote islands, home care had been recommended by medical staff. CONCLUSION: It is important for professionals coordinating home care to understand the characteristics of diseases, perform early assessment of caregiver situations, and collaborate with medical staff.

The effect of ropinirole on apathy and depression after herpes encephalitis.

We describe a 76-year-old man with herpes encephalitis whose symptom of severe apathy was improved by the dopamine D2/D3 receptor agonist ropinirole. Brain magnetic resonance imaging had shown lesions in the patient's right mesial temporal cortex, right insula, and bilateral medial frontal regions. During treatment with acyclovir, he had developed severe apathy and depression. On neuropsychological assessment, he scored 21/30 points on the Mini-Mental State Examination, 30/42 on the Starkstein Apathy Scale (cutoff score =16), and 59/80 on the Zung Self-Rating Depression Scale (cutoff score=40). We then started him on ropinirole 0.25 mg/day. Over the next 10 days, his apathy and depression gradually improved. On day 10 of treatment, follow-up testing showed that his Apathy Scale score had improved to 25 points. This case suggests that a low dose of a dopamine receptor agonist may be an effective treatment for patients who develop apathy and depression after encephalitis.

Hypertension and Advanced Age Increase the Risk of Cognitive Impairment after Mild Traumatic Brain Injury: A Registry-Based Study.

BACKGROUND: As the global population ages, the incidence of traumatic brain injury (TBI) is increasing. Whereas mild TBI can impair the cognitive function of older adults, the cause and background of mild TBI-induced cognitive impairment remain unclear, and the evaluation of risk factors for cognitive impairment after mild TBI remains open for consideration, especially in the aging population. This study aimed to evaluate the risks associated with cognitive impairment following mild TBI. METHODS: Between January 2006 and December 2018, a total of 2209 patients with TBI required hospitalization in Shimane Prefectural Central Hospital. Mild TBI was defined as a Japan Coma Scale ≤10 at admission. Patients' cognitive function was measured with the Hasegawa Dementia Rating Scale-Revised or Mini-Mental State Examination at least twice during the patients' hospital stays. The odds ratio (OR) and 95% confidence interval (CI) of each considered risk factor was calculated with multivariable logistic regression analysis after univariate analysis. RESULTS: Among 1674 patients with mild TBI, 172 patients underwent cognitive function examinations, of whom 145 (84.3%) were found to have cognitive impairment at discharge. Significant risk factors for cognitive impairment included age (P = 0.008) and hypertension (P = 0.013) in univariate analysis; and age (OR, 1.04: 95% CI, 1.01-1.07) and hypertension (OR, 5.81: 95% CI, 1.22-27.68) by multivariable analysis. CONCLUSIONS: Older patients with hypertension displayed a significantly higher risk for cognitive impairment after even mild TBI. These patients warrant careful management after even mild TBI.

Health management of adults with Turner syndrome: an attempt at multidisciplinary medical care by gynecologists in cooperation with specialists from other fields.

AIM: Since women with Turner Syndrome (TS) have various complications, they require comprehensive medical evaluation and multidisciplinary treatment. Although TS patients receive adequate care in childhood, many adults with TS do not. Since most TS adults attend gynecologists for hormone replacement therapy, we suggest gynecologists take primary responsibility for their management. In an attempt to provide TS patients with a comprehensive treatment regimen, we started multidisciplinary medical management in the Reproductive Health Clinic at Yokohama City University Hospital. To evaluate the efficacy of this medical care system, a retrospective analysis was conducted. METHODS: The clinical profiles of 57 TS patients were examined. The past histories, complications and clinical data of these patients were extracted from their medical records and examined clinically. Bone mineral density measurements of lumbar vertebrae (L(2-4)), anti-thyroid antibody titer measurements, hearing tests and cardiovascular MRI were also performed. RESULTS: Mean follow-up duration was 5.1 years (range, 1-8 years). At the time of transition, patients with complications developed in childhood, such as amenorrhea, osteopenia/osteoporosis, otitis media, thyroid dysfunction and cardiovascular disease were identified. All these complaints were successfully followed up in our adult care system. Several complications common to TS adults, such as glucose intolerance, liver dysfunction, hyperlypidemia and hypertension could be identified by our screening system. Patients were referred to specialists when necessary. CONCLUSION: Multidisciplinary health management in our Reproductive Health Clinic improved the status of medical care for TS adults.

Congenital omphalocele and polyhydramnios: a study of 52 cases.

INTRODUCTION: Unlike gastroschisis, congenital omphalocele is often associated with other anomalies and is frequently complicated by polyhydramnios. We examined the relationships between polyhydramnios, pregnancy outcome and fetal prognosis. PATIENTS AND METHODS: Clinical data from cases diagnosed antenatally with congenital omphalocele from 1993 to 2006 were analyzed retrospectively. RESULTS: Fifty-two cases were diagnosed antenatally with congenital omphalocele, and 38 of these pregnancies resulted in delivered infants. Of these 38 pregnancies, 55.3% were preterm births before 37 weeks of gestation. The mean birth weight was 2,148 g (n = 38). Associated anomalies were recognized in 29 cases (76.3%), including 13 cases (34.2%) of chromosomal aberrations. There were 2 cases of trisomy 13, 10 cases of trisomy 18 and 1 case of trisomy 21. Polyhydramnios was detected in 14 cases (36.8%), and other anomalies were present in all of these cases. DISCUSSION: For antenatal evaluation in cases of congenital omphalocele, it is important to examine the fetus for associated anomalies or underlying disease, especially when polyhydramnios is detected.

Tris(pyridin-2-yl-methanol)nickel(II) hexa-fluoridophosphate trifluoro-acetate.

In the crystal structure of the title complex, [Ni(C(6)H(7)NO)(3)](PF(6))(C(2)F(3)O(2)), the Ni(II) ion is in a slightly distorted octa-hedral NiO(3)N(3) coordination geometry with each of the three N and three O atoms in a meridional coordination. In the crystal, the complex mol-ecules and the trifluoro-acetate anions are connected via O-H⋯O hydrogen bonding into layers parallel to the ab plane.

Dietary soybean oil, canola oil and partially-hydrogenated soybean oil affect testicular tissue and steroid hormone levels differently in the miniature pig.

The present study was conducted to examine the influence of dietary canola oil (CAN) and partially-hydrogenated soybean oil (HSO) compared to soybean oil (SOY, control) on the morphology and function of testes using miniature pigs as the test subject. Male miniature pigs were fed a diet containing 10%SOY, 9%CAN+1%SOY, or 9%HSO+1%SOY for 18 months. The scheduled autopsies revealed no abnormalities in histopathological examination of the major organs, except the testes. Atrophy of the seminiferous tubules and hyperplasia in the Leydig cells were found in the SOY and CAN groups. DNA microarray analysis indicated downregulation in the CAN and the HSO groups of genes encoding for gonadotropins in the pituitary gland and of enzymes and proteins involved in steroid hormone metabolism in the testes, compared to the SOY group. Plasma levels of sex hormones in the CAN and HSO groups tended to be higher and testosterone and dihydrotestosteorne in the HSO group were significantly higher than in the SOY group. These results demonstrate that testes are morphologically and functionally affected by the dietary oils, while the plasma steroid hormone levels do not necessarily reflect the gene expression, probably owing to feedback regulation via the gonadal hormones in the hypothalamus-pituitary-gonadal axis.

Different effects of 26-week dietary intake of rapeseed oil and soybean oil on plasma lipid levels, glucose-6-phosphate dehydrogenase activity and cyclooxygenase-2 expression in spontaneously hypertensive rats.

We intended to determine whether or not dietary canola oil (CO) elevates plasma lipids and oxidative stress, since both of these are, possibly, related to the CO-induced life shortening through exacerbation of hypertension-associated vascular lesions found in stroke-prone spontaneously hypertensive rats (SHRSP). Spontaneously hypertensive rats (SHR) were used in this study to avoid a potential bias in the results due to the irregular death by stroke seen in SHRSP. SHR were fed for 26 weeks on a chow containing either, 10 wt/wt% of CO or soybean oil (SO), i.e., the control. Elevated plasma lipids and glucose-6-phosphate dehydrogenase (G6PD) activation in the liver and erythrocyte were found in SHR fed CO compared to that fed SO, while anti-oxidative enzymes other than G6PD were not activated. The CO diet brought about significant vascular lesions in the kidney, in which abundant cyclooxygenase-2 (COX-2) positive foci were immunochemically located in the juxtaglomerular apparatus. These results suggest that dietary CO induces a hyperlipidemic condition, in which G6PD may serve as an NADPH provider, and aggravates genetic diseases in SHR (also, probably, in SHRSP). The increased COX-2 expression indicates a role of renin-angiotensin-aldosterone system activation in the increased vascular lesions, whereas the effects of oxidative stress remain unclear.

The evaluation of early embryonic neurogenesis after exposure to the genotoxic agent 5-bromo-2'-deoxyuridine in mice.

Developmental neurotoxicity (DNT) is an important issue in children's health. Neurogenesis occurs throughout the early fetal to the postnatal period. The proliferation of embryonic stem cells can be a target for toxicants, especially genotoxic compounds. 5-Bromo-2'-deoxyuridine (BrdU), a thymidine analogue, has been used as a marker for proliferating cells. However, we reported that prenatal BrdU exposure induced behavioral abnormalities such as hyperactivity in rat and mouse offspring. In this study, to further clarify the toxic effect of BrdU on the early neurogenesis and to examine the usefulness of the evaluation of this process in DNT, C57BL/6 mice were exposed to 100 mg/kg of BrdU once on gestational day (GD) 9 or 11, and serial sections from a wide variety of areas of the embryonic brains 24 h after the exposure were examined. BrdU exposure on GD11 induced cell death in some specific areas, such as the neocortex and striatum, but not in the substantia nigra, raphe and pons, even though BrdU was incorporated into those cells. BrdU decreased the number of cells positive for phosphorylated histone 3 (phospho-histone 3), a marker for proliferating cells at metaphase of mitosis, in the cortex, mammillary body and cerebellum, suggesting that BrdU affected the proliferation of neural stem cells. Exposure on GD9 did not induce cell death in the fetal brain. These results indicate that BrdU actually impaired the early neurogenesis, supporting the postnatal results, and demonstrated that embryonic neurogenesis has heterogeneous sensitivity to the genotoxic agents BrdU that differs according to the area and developmental stage. The evaluation of events in early neurogenesis such as the proliferation of neural stem cells shortly after chemical exposure will be one of the valuable endpoints for studying postnatal neurodevelopmental disorders.

A ninety-day feeding, subchronic toxicity study of oligo-N-acetylglucosamine in Fischer 344 rats.

Oligo-N-acetylglucosamine (OAG) is a hydrolyzed derivative of chitin that has been used as a sweetener in foods. Since, no information has been published about the safety of OAG, a 90-day feeding study was conducted, using F344 Fischer rats of both sexes, to characterize and evaluate the toxicity of OAG, and the results of the study are presented here. Dietary levels of 0% (control), 0.2%, 1%, and 5% OAG did not change any measurements in ophthalmological examinations, clinical signs, body weights, food consumption, hematology, blood biochemistry, urinalysis, necropsies, organ weights or histological examinations. The sole finding, which could not be clarified to be attributed to OAG or not, was a decrease in the relative weight of the submaxillary gland to body weight in the male animals given the 5% OAG diet. Although no lesions were found in either gross or histological examination in the present study, further studies using OAG levels higher than 5% might provide a clue to the mechanisms underlying the decreased organ weight observed here. Taken together, under the conditions in the present study, the No Observed Adverse Effect Level (NOAEL) for males was found to be 1% (0.641 g/kg/day); and that for females, 5% (3.64 /kg/day) or more, based on the lack of toxicological effects.

A 90-day ad libitum administration toxicity study of oligoglucosamine in F344 rats.

A 90-day ad libitum administration toxicity study of oligoglucosamine (OG) was carried out using F344 rats of both sexes. The animals were divided into four groups of 20 animals each, 10 of each sex, and fed a diet containing 0, 0.04, 0.2 or 1.0 (w/w)% OG. During the administration period, no animals of either sex died or exhibited abnormal signs in the 0.04% OG and 0.2% OG groups. In the 1% OG group, in both sexes, erythema and swelling of the snout and forelimbs and loss of fur in the forelimbs were observed. On macroscopic observation, emaciation, swelling of the snout, auricles and forelimbs and alopecia of the forelimbs were also observed in 2-3 males of the 1% OG group. It was suggested that these topical abnormalities might be due to dermal responses to OG adhering to the skin and fur, which are easily soiled with saliva during grooming. In the animals of the 1% OG group, food consumption decreased, resulting in body weight gain being suppressed. This was found concomitantly with the abnormal findings mentioned above. Thus, feeding difficulties due to the topical lesions on the snout and forelimbs were thought to affect body weight. In hematology, platelet count, lymphocyte count and differential neutrophil count increased in males of the 1% OG group. These changes might be related to the dermal inflammation. Abnormalities in urinalysis and blood chemistry, as well as a small thymus, small spleen, dark spots or areas on the glandular stomach mucosa, pale Harderian glands and small testes in histopathology, were also observed in males in the 1% OG group. Whether or not all these changes were related only to the malnutrition remains to be elucidated. From these results, OG gave rise to no adverse effects in rats up to the dose level of 0.2 (w/w)%. Thus, the no observed adverse effect level was determined to be 0.2 (w/w)% for rats of either sex (124.0mg/kg/day in males, 142.0mg/kg/day in females).

pH-Dependent structural diversity of a 2-pyridinemethanol Cu complex and its relatively strong magnetic exchange coupling via hydrogen bonding.

The diversity of the self-assembled structures of a Cu complex via hydrogen bonding, including a square planar unit, is reported. The Cu complex forms two self-assembled structures by hydrogen bonding, depending on the acidity of the recrystallization conditions. A linear chain structure can be produced under acidic conditions, and a three-dimensional network structure is observed under basic conditions. The linear chain structure is constructed from intermolecular sharing of a hydrogen atom between two 2-pyridinemethanolate units, with an OO distance of 2.412(1) Å and an O-H-O bond angle of 170(3)°. The linear chain structure exhibits relatively strong magnetic coupling (J = -9.91(2) cm-1) via hydrogen bonding between Cu atoms; this coupling was also confirmed by electron spin resonance experiments. Thermochromic behavior was also observed for the complex.

Efficacy of Fibroblast Growth Factor on Epithelialization of the Neovagina in Patients with Mayer-Rokitansky-Küster-Hauser Syndrome Who Underwent Vaginoplasty.

STUDY OBJECTIVE: To evaluate the effect of fibroblast growth factor (FGF) on epithelialization of neovagina in patients with Mayer-Rokitansky-Küster-Hauser syndrome who underwent vaginoplasty. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Seven patients with Mayer-Rokitansky-Küster-Hauser syndrome. INTERVENTIONS: Cytological examination was done on vaginal smear samples from the site of completed epithelialization, and tissue was collected from the epithelialized part for histological evaluation. Immunostaining for estrogen receptor α, and keratin 13 and 14, and reverse transcription polymerase chain reaction (RT-PCR) analysis of the FGF receptor (FGFR) 1-4 were performed in samples from case 2 three times (ie, during the surgery, during the period of vaginal creation, and at 3 months and 6 months after the surgery). MAIN OUTCOME MEASURES: The primary outcome was the FGF effects on the epithelialization speed and FGFR expression in the neovagina. The second was the role of FGF in the mechanism of vaginal epithelial cell proliferation. RESULTS: The histological structure of the neovagina was consistent with that of normal vagina. RT-PCR analysis revealed that FGFR was expressed in the control vaginas and neovaginas. Among the FGFR subtypes, FGFR-4 was overexpressed during the process of epithelialization and its level decreased after completion of creation of the new vagina. CONCLUSION: The epithelium of the neovagina was morphologically similar to that of normal vagina. It is suggested that FGF plays the role as a growth factor.