Peripheral administration of κ-opioid receptor antagonist stimulates gonadotropin-releasing hormone pulse generator activity in ovariectomized, estrogen-treated female goats.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is indispensable for reproduction in mammals. Kisspeptin neurons in the hypothalamic arcuate nucleus (ARC), referred to as KNDy neurons because of the coexpression of neurokinin B and dynorphin A, are considered as components of the GnRH pulse generator that produces rhythmic GnRH secretion. The present study aimed to investigate if peripheral administration of PF-4455242, a κ-opioid receptor (KOR, a dynorphin A receptor) antagonist, facilitates pulsatile luteinizing hormone (LH) secretion and GnRH pulse generator activity in estrogen-treated ovariectomized Shiba goats to determine the possibility of using KOR antagonists to artificially control ovarian activities. PF-4455242 was intravenously infused for 4 h (1 or 10 µmol/kg body weight/4 h) or as a single subcutaneous injection (1 or 10 µmol/kg body weight). In a separate experiment, the same KOR antagonist (10 µmol/kg body weight/4 h) was intravenously infused during the recording of multiple unit activity (MUA) in the ARC that reflects the activity of the GnRH pulse generator to test the effects of KOR antagonist administration on GnRH pulse generator activity. Intravenous infusion and single subcutaneous injection of the KOR antagonist significantly increased the frequency of LH pulses compared with controls. Intravenous infusion of KOR antagonist also significantly increased the frequency of episodic bursts in the MUA. The present study demonstrates that peripherally administered KOR antagonist stimulates pulsatile LH secretion by acting on the GnRH pulse generator, and peripheral administration of PF-4455242 can be used to facilitate pulsatile LH secretion, which in turn facilitates ovarian activities in farm animals.

Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones.

Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18ß-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling enhances synchronised activities among neighbouring KNDy neurones, and that both neurone-neurone and neurone-glia communications via gap junctions possibly contribute to synchronised activities among KNDy neurones.

Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans.

BACKGROUND/OBJECTIVES: Brown adipose tissue (BAT) is a potential therapeutic target against obesity and diabetes through thermogenesis and substrate disposal with cold exposure. The role of BAT in energy metabolism under thermoneutral conditions, however, remains controversial. We assessed the contribution of BAT to energy expenditure (EE), particularly diet-induced thermogenesis (DIT), and substrate utilization in human adults. METHODS: In this cross-sectional study, BAT activity was evaluated in 21 men using 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) after cold exposure (19 °C). The subjects were divided into BAT-positive (n=13) and BAT-negative (n=8) groups according to the 18F-FDG-PET/CT findings. Twenty-four hour EE, DIT and respiratory quotient were measured using a whole-room indirect calorimeter at 27 °C. RESULTS: Body composition, blood metabolites and 24-h EE did not differ between groups. DIT (%), calculated as DIT divided by total energy intake, however, was significantly higher in the BAT-positive group (BAT-positive: 9.7±2.5%, BAT-negative: 6.5±4.0%, P=0.03). The 24-h respiratory quotient was significantly lower (P=0.03) in the BAT-positive group (0.861±0.027) than in the BAT-negative group (0.889±0.024). CONCLUSION: DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.

Synpolydactyly of the hand: a radiographic classification.

UNLABELLED: Synpolydactyly is an uncommon congenital anomaly characterized by polydactyly with syndactyly in the central hand. The purpose of this investigation was to develop and assess the reliability of a radiographic classification system for synpolydactyly. We identified 56 hands with central synpolydactyly and developed a radiographic classification system that categorizes by the location within the hand, the bony level of polydactyly, and the presence of a delta phalanx. Four paediatric hand surgeons independently reviewed each radiograph to establish reliability. There was exact agreement among raters in 40 cases (71%). The inter-rater reliability was 0.97 and intra-rater reliability was at least 0.87. Seven of 16 bilateral cases had symmetric deformity classification. The most common presentations were types 1A and 2A. We present a new, reliable radiographic classification system for synpolydactyly that will allow improved communication between clinicians and serve as a foundation for future investigations. LEVEL OF EVIDENCE: 2.

Large-scale psychological differences within China explained by rice versus wheat agriculture.

Cross-cultural psychologists have mostly contrasted East Asia with the West. However, this study shows that there are major psychological differences within China. We propose that a history of farming rice makes cultures more interdependent, whereas farming wheat makes cultures more independent, and these agricultural legacies continue to affect people in the modern world. We tested 1162 Han Chinese participants in six sites and found that rice-growing southern China is more interdependent and holistic-thinking than the wheat-growing north. To control for confounds like climate, we tested people from neighboring counties along the rice-wheat border and found differences that were just as large. We also find that modernization and pathogen prevalence theories do not fit the data.

PP077. Effect of maternal antioxidant concentrations on expressions of angiogenesis-related genes in the villous trophoblasts from early pregnancy.

INTRODUCTION: The pathogenesis of preeclampsia is associated with oxidative stress of villous trophoblasts in early pregnancy. We have reported that antioxidant supplementations from 12weeks of gestation could prevent mild preeclampsia in pregnant women with oxidative stress. OBJECTIVES: To prove the effect of maternal antioxidant concentrations on expressions of angiogenesis-related genes in the villous trophoblasts from early pregnancy. METHODS: Villous tissue and blood samples were obtained from pregnant women who had artificial abortions between 6 and 11weeks of gestation. RNA was extracted from villous tissue, and gene expression levels of fms-like tyrosine kinase-1 (FLT-1), endoglin (ENG), and placental growth factor (PGF) in villous tissue were measured by reverse transcription polymerase chain reaction. Serum vitamin C and E concentrations were measured by enzyme-linked immunosorbent assay. This study was approved by the Ethics Committee of Showa University Hospital. RESULTS: Negative correlations between maternal serum vitamin C levels and gene expressions of ENG (r=-0.856, p=0.007) and FLT-1 (r=-0.898, p=0.002) in the villous trophoblasts were observed. There was no correlation of maternal serum vitamin E concentration with any other gene expression in the villous trophoblasts. CONCLUSION: It is suggested that maternal oxidative stress may increase the gene expressions of anti-angiogenic factors in villous trophoblasts of early gestation, which may lead to the pathogenesis of preeclampsia.

WE-G-217BCD-06: Fully Incorporated Scanning Geometry for Improved Accuracy in C-Arm CBCT Image Reconstruction.

PURPOSE: The adoption of C-arm cone-beam CT (CBCT) can minimize interruption to the interventional workflow. However, C-arm gantry rotation can be susceptible to gravity and mechanical instability, therefore resulting images with contamination of tilting and wobbling motion. The purpose of this work is to investigate and demonstrate potential improvement of C-arm CBCT images by tailoring and applying an innovative iterative algorithm that can fully incorporate accurate scanning geometry. METHODS: A clinical C-arm CBCT system (Toshiba Infinix-i, Japan) was used for collecting projection data of a patient's brain with aneurysm. A mask scan was performed before contrast was injected, and a contrast scan was performed during continuous contrast feeding. During each scan, 108 projections were acquired over a range of approximately 200 degrees within about 4.6 seconds. Logarithm subtraction was then carried out view by view to obtain 108 projections of virtually only the vasculature. An iterative algorithm, referred to as the ASD-POCS algorithm, was modified to fully incorporate calibration data characterizing the actual scan geometry that deviates from a circular trajectory due to gantry tilting and wobbling. We then applied both FDK and ASD-POCS algorithms to reconstructing image from the acquired patient data. RESULTS: In FDK reconstructions without considering C-arm tilting and wobbling motion, artifacts can be observed, which break vessel continuity and compromise image's clinical utility. We then performed FDK reconstructions by incorporating the system geometry in the back-projection step and obtained improved vessel continuity. Finally we applied the ASD- POCS algorithm by incorporating calibration data in the forward- and back- projector, and obtained reconstructions with further improvement on the recovery of small, secondary vascular branches. CONCLUSIONS: Appropriately developed iterative algorithms can improve C-arm CBCT image quality by fully incorporating scanning geometry, and can potentially enable spatial-resolution demanding applications which can be challenging to achieve with the FDK algorithm.

High pressure investigations of Na0.025WO3: x-ray diffraction and Raman spectroscopy studies.

High pressure x-ray diffraction and Raman spectroscopy studies have been carried out on non-stoichiometric sodium tungsten bronze, Na(0.025)WO(3). The high pressure investigations reveal a phase transition at about 2 GPa by a change of space group symmetry from P2(1)/n to P2(1)/c in the monoclinic cell followed by a second structural transformation to a triclinic lattice around 18 GPa. There are volume changes with these structural transformations, which are driven by rotation and significant distortion of WO(6) octahedra due to the displacement of tungsten and oxygen atoms from their mean positions in the unit cell.

Cellular locations of proteinases and association with vesicles in Porphyromonas gingivalis.

We found that locations of arginine-specific gingipain (RGP) in the cellular fractions in the crude extract, envelope, vesicles, and culture supernatants were 48%, 16%, 17%, and 31%, respectively, and the corresponding values of lysine-specific gingipain (KGP) were 47%, 10%, 7%, and 36%, respectively. Although the molecular mass of RGP in the culture supernatant had been determined as 43 kDa, and that of KGP had been as 48 kDa, molecular masses of both proteinases solubilized from the vesicles were estimated to be over 1,500 kDa, since they eluted in the void volume of the column in the gel filtration on Sephacryl S-300. There was no reduction of molecular size by the following treatment with SDS, high-concentration NaCl, or urea. Interestingly, the occurrence of the macromolecular forms could not observed in other enzymes tested such as monopeptidyl, dipeptidyl, and tripeptidyl peptidases, as well as alkaline phosphatase. Therefore, occurrence of the macromolecular forms may be restricted to the proteinases. When the vesicle and culture supernatants containing free RGP and KGP were mixed and incubated, neither RGP nor KGP seemed to bind to vesicles. RGP bound to the vesicle was found to be more stable to heat treatment than the free form, suggesting that association of RGP with the vesicle caused heat stability of this enzyme.

Hemoglobin binding activity and hemoglobin-binding protein of Prevotella nigrescens.

Prevotella nigrescens, lacking siderophores was found to bind to the hemoproteins. The binding was observed also in the envelope which was prepared by sonication of the cell. The binding occurred in the pH-dependent manner; the binding was observed below neutral pHs of the incubation mixtures but only slightly observed in the neutral and alkaline pHs. Furthermore, hemoglobin bound to the envelope was dissociated at high pHs buffers. Maximum amounts of hemoglobin bound to 1 mg envelope was 51.2 mug. Kd for the reaction at pH 5.0 was 2.1 x 10¹° M (210 pM). From the dot blot assay, hemoglobin could bind to a protein solubilized from the envelope by a detergent, referred to as hemoglobin-binding protein (HbBP), then it was purified by the sequential procedures of ion exchange chromatography, affinity chromatography and isoelectric focusing. Molecular weight and isoelectric point of the HbBP were 46 kDa and 6.1, respectively.

The experience of burnout among home caregivers of patients with dementia: relations to depression and quality of life.

Caregivers of patients with dementia often experience chronic and emotional strains, which may lead to emotional exhaustion and burnout. The objective of this study was to examine the relationships between burnout, depression, and quality of life in home caregivers of patients with dementia. The participants were 84 home caregivers (39 male; 45 female), and they were asked to complete three questionnaires: the Beck Depression Inventory Second Edition (BDI-II), the WHO Quality of Life 26 (WHO-QOL26), and the Pines Burnout Measure (BM). Results from a bivariate correlation showed that BM scores significantly correlated with the scores on BDI-II and WHO-QOL26. Results from ANOVA comparing the level of burnout with the scores on BDI-II and WHO-QOL26 revealed that there were differences between the burnout groups and the scores on BDI-II and WHO-QOL26. The higher levels of burnout were found to correspond to higher levels of depressive symptoms and lower QOL. These findings suggest that caregiver intervention to reduce burnout might benefit from strategies to reduce depression and increase QOL.

Angle-resolved photoemission spectroscopy of the insulating NaxWO3: Anderson localization, polaron formation, and remnant Fermi surface.

The electronic structure of the insulating sodium tungsten bronze, Na(0.025)WO(3), is investigated by high-resolution angle-resolved photoemission spectroscopy. We find that near-E(F) states are localized due to the strong disorder arising from random distribution of Na+ ions in the WO(3) lattice, which makes the system insulating. The temperature dependence of photoemission spectra provides direct evidence for polaron formation. The remnant Fermi surface of the insulator is found to be the replica of the real Fermi surface in the metallic system.

Psychiatric, somatic, and gastrointestinal disorders, and Helicobacter pylori infection in children with recurrent abdominal pain.

AIMS: To examine the utility of the Rome II criteria in children with recurrent abdominal pain (RAP) and compare them to those who met Apley's criteria and those who met neither criteria. METHODS: Prospective study in general paediatric clinics in Komagane, Japan. Children with abdominal pain were classified into those who met Rome II criteria, those who met Apley's criteria, and those who met neither. RESULTS: A total of 182 children with RAP participated; 45 children met Rome II criteria, 55 met Apley's criteria, and 82 met neither. Children who met Rome II criteria had a significantly higher prevalence of psychiatric and somatic disorders compared to the group met neither (36% v 6%, 22% v 10%, respectively). The overall prevalence of H pylori was 7%; prevalence increased with age from 3% at age < or = 10 to 10% for children >10 years. Children who met Rome II criteria had a significantly higher prevalence of H pylori infection than the reference group (18% v 4%). In a logistic regression model, all the study variables were included in the model specifying first the Rome II criteria group as the independent variable; psychiatric disorders, H pylori infection, and older age group were independent risk factors. CONCLUSIONS: More than half the children suffering from recurrent abdominal pain met neither Apley's nor Rome II criteria. Children who meet Rome II criteria should be evaluated for psychiatric disorders and should be tested for H pylori infection. Despite the overall trend for a fall in the prevalence of H pylori infection among children in Japan, there are subpopulations of sick children where the prevalence of the infection is relatively high.

Testicular toxicity of dietarily or parenterally administered bisphenol A in rats and mice.

Male Crj:Wistar rats, HsdHot:Holtzman SD rats, Crj:CD-1(ICR) mice and C57BL/6CrSlc mice were administered bisphenol A (BPA) in the diet at a level of 0 (control) and 0.25% for 8 weeks. Daily BPA intake was about 200 and 400 mg/kg for rats and mice, respectively. No conspicuous signs of general or reproductive toxicity were observed after administration in any strain of these animals. Serum testosterone concentrations were not decreased in BPA-fed rats and mice. Successive subcutaneous administration of BPA at a dose of 200 mg/kg/day for 4 weeks significantly decreased the testis, epididymis, prostate and seminal vesicle weights, and the testicular daily sperm production in Jcl:Wistar rats. Successive intraperitoneal administration of BPA at a dose of 20 mg/kg/day for 4 weeks decreased the prostate and seminal vesicle weights but not the testis or epididymis weights. An intraperitoneal dose of 2 mg BPA/kg/day did not cause any toxicity. These results indicate that dietarily administered BPA is less toxic to most strains of rats and mice, and the maximum non-toxic dose and/or minimum toxic dose may be about 200 mg/kg/day. Subcutaneous or intraperitoneal BPA is much more toxic on male reproductive and sex accessory organs than dietary.

Effects of propyl paraben on the male reproductive system.

Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives in foods, cosmetics, toiletries and pharmaceuticals. These compounds exert a weak estrogenic activity as determined by in vitro estrogen receptor assay and in vivo uterotrophic assay. In a previous study, it was demonstrated by the present author that exposure of post-weaning mammals to butyl paraben adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that propyl paraben also adversely affects the hormonal secretion and the male reproductive functions. Propyl paraben was administered to 3-week-old rats which were divided into four groups of eight animals each, at doses of 0.00, 0.01, 0.10 and 1.00% with the AIN93G modified diet. At the end of 4 weeks, the rats were sacrificed by decapitation and the weights of testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of propyl paraben on the organ weights in any of the study groups. The cauda epididymal sperm reserves and concentrations decreased in a dose-dependent manner and the difference was significant at dose of 0.10% and above. Daily sperm production and its efficiency in the testis of all groups receiving propyl paraben significantly decreased. The serum testosterone concentration decreased in a dose-dependent manner and the decrease was significant in the group that received the highest dose. The exposure level at which this effect was observed is the same as the upper-limit acceptable daily intake (10 mg/kg body weight/day) of parabens in the European Community and Japan.

Detectability of pulmonary perfusion defect and influence of breath holding on contrast-enhanced thick-slice 2D and on 3D MR pulmonary perfusion images.

The present study assesses the detectability of perfusion defect and the influence of breathhold on pulmonary magnetic resonance (MR) perfusion imaging using contrast-enhanced thick-slice two-dimensional (2D) fast gradient-echo sequence compared with three-dimensional (3D) fast spoiled gradient-recalled sequence. Dynamic studies were performed in 16 patients. MR perfusion images were interpreted by two independent observers using perfusion scintigraphy as the reference standard. The patients were divided into two groups according to the duration of holding the breath measured during MR imaging. The sensitivity and specificity of 2D MR perfusion imaging in detecting perfusion defects were 93% and 94%, respectively, while those of 3D MR perfusion imaging were 89% and 85%, respectively. The diagnostic accuracy of 2D MR perfusion imaging was significantly higher than that of 3D MR perfusion imaging (P < 0.05) among those who could not hold their breath. Therefore, 2D MR perfusion imaging offers promise for evaluating pulmonary perfusion even among patients who cannot hold their breath.

A synchrotron X-ray study of triclinic LiCa2Nb3O10 with perovskite-type slabs.

The triclinic superstructure of a small crystal of LiCa(2)Nb(3)O(10), lithium dicalcium triniobium decaoxide, has been investigated by synchrotron X-ray diffraction. The unit cell is an almost rectangular parallelepiped, although there is a 0.245 degrees offset from orthogonality for beta. The structure essentially belongs to a homologous series of Li[Na(n-3)Ca(2)Nb(n)O(3n+1)] with n = 3, where the moiety in square brackets has a perovskite-type slab structure. The superstructure has a doubled unit-cell volume with respect to the tetragonal aristotype. The NbO(6) octahedra are rotated about axes parallel to [110] by approximately 10 degrees. Adjacent slabs are connected by Li atoms and are geometrically related by 4(2) pseudosymmetry lying parallel to c. There are twice as many sites as Li atoms, providing a variation of population at these Li sites.

[Subacute cor pulmonale due to microscopic pulmonary tumor embolism].

We report a case of subacute pulmonary hypertension caused by microscopic pulmonary tumor embolism due to the dissemination of gastric cancer cells. The patient, a 61-year-old man with no history of malignant diseases, was admitted to our hospital on October 14 in 1998 because of cough and dyspnea on effort, that had developed since the previous month. On admission, chest radiography including CT scans showed slight cardiomegaly and disseminated reticulonodular shadows predominating in the lower lung fields of both lungs, and arterial blood gas analysis disclosed severe hypoxemia. Lung perfusion scintigraphy revealed multiple irregular defects in both lungs. Echocardiography indicated right ventricular overload, and the pulmonary artery systolic pressure was estimated to be higher than 80 mmHg. Disseminated intravascular coagulation (DIC) developed on the 6th day of hospitalization. Multiple pulmonary embolism with DIC of unknown cause was diagnosed, and the patient was given anticoagulant therapy with heparin. However, he died of respiratory failure on the 7th day of hospitalization. At autopsy, an invasive cancer was found in the stomach, resembling type IIc early gastric cancer. The lumens of the pulmonary arterioles were significantly narrowed by fibrocellular proliferation and thrombi accompanying tumor cell clusters, and some of the microvessels were completely occluded. Disseminated microscopic pulmonary metastasis of malignant tumors should be included in the differential diagnosis of subacute pulmonary hypertension due to multiple pulmonary embolism of unknown cause.

Re-examining the general positivity model of subjective well-being: the discrepancy between specific and global domain satisfaction.

Three studies were conducted to examine the role of global life satisfaction in the discrepancy between specific and global domain satisfaction. Participants rated both global (e.g., education) and the corresponding, specific domain (e.g., professors, textbooks) satisfactions. In 3 studies, we found that individuals with higher life satisfaction evaluated global domain as a whole as more satisfying than those with lower life satisfaction, given the same level of satisfaction with specific domains. In Study 3, we also found that, given the same level of satisfaction during the previous 2 weeks, individuals with higher life satisfaction rated the global domains in general as more satisfying than those with lower life satisfaction. Overall, the association between globallife satisfaction and evaluative enhancement of global domains was most consistent in "self" and "social relationships." Finally, the effect of global life satisfaction on evaluative enhancement remained significant, controlling for extraversion and neuroticism.

Improving primary care for depression in late life: the design of a multicenter randomized trial.

BACKGROUND: Late life depression can be successfully treated with antidepressant medications or psychotherapy, but few depressed older adults receive effective treatment. RESEARCH DESIGN: A randomized controlled trial of a disease management program for late life depression. SUBJECTS: Approximately 1,750 older adults with major depression or dysthymia are recruited from seven national study sites. INTERVENTION: Half of the subjects are randomly assigned to a collaborative care program where a depression clinical specialist supervised by a psychiatrist and a primary care expert supports the patient's regular primary care provider to treat depression. Intervention services are provided for 12 months using antidepressant medications and Problem Solving Treatment in Primary Care according to a stepped care protocol that varies intervention intensity according to clinical needs. The other half of the subjects are assigned to care as usual. EVALUATION: Subjects are independently assessed at baseline, 3 months, 6 months, 12 months, 18 months, and 24 months. The evaluation assesses the incremental cost-effectiveness of the intervention compared with care as usual. Specific outcomes examined include care for depression, depressive symptoms, health-related quality of life, satisfaction with depression care, health care costs, patient time costs, market and nonmarket productivity, and household income. CONCLUSIONS: The study blends methods from health services and clinical research in an effort to protect internal validity while maximizing the generalizability of results to diverse health care systems. We hope that this study will show the cost-effectiveness of a new model of care for late life depression that can be applied in a range of primary care settings.