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Background: Our objective was to evaluate risks of adverse obstetric outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy.Methods: We analyzed the national health insurance database, which covers almost the entire Korean population, between 2004 and 2015. The risks of adverse pregnancy outcomes in pregnancies with myoma(s) or in pregnancies following myomectomy, compared to those in women without a diagnosed myoma, were analyzed in multivariate logistic regression analysis.Results: During the study period, 38,402 women with diagnosed myoma(s), 9890 women with a history of myomectomy, and 740,675 women without a diagnosed myoma gave birth. Women with a history of diagnosed myoma(s) and women with a history of myomectomy had significantly higher risks of cesarean section (aOR 1.13, 95% CI 1.1-1.16 and aOR 7.46, 95% CI 6.97-7.98, respectively) and placenta previa (aOR 1.41, 95% CI 1.29-1.54 and aOR 1.58, 95% CI 1.35-1.83, respectively), compared to women without a diagnosed myoma. And the risk of uterine rupture was significantly higher in women with previous myomectomy (aOR 12.78, 95% CI 6.5-25.13), compared to women without a diagnosed myoma, which was much increased (aOR 41.35, 95% CI 16.18-105.69) in nulliparous women. The incidence of uterine rupture was the highest at delivery within one year after myomectomy and decreased over time after myomectomy.Conclusions: Women with a history of myomectomy had significantly higher risks of cesarean section and placenta previa compared to women without a diagnosed myoma. [ABSTRACT FROM AUTHOR]

Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1. • Ultrasound-induced neuromodulation is initiated by opening of TRPA1 in astrocytes • The Ca2+ entry through TRPA1 causes a release of glutamate through Best1 channels • The released glutamate activates NMDA receptors in neighboring neurons Oh et al. show that TRPA1 is the molecular sensor and transducer for low-intensity, low-frequency ultrasound (LILFU). With TRPA1's unique co-localization and cooperation with the glutamate-releasing Ca2+-activated Best1 at the microdomains of astrocytes, LILFU is capable of eliciting neuromodulation as a consequence of neuronal NMDAR activation. [ABSTRACT FROM AUTHOR]

Multiple studies have shown that astrocytes in the medullary dorsal horn (MDH) play an important role in the development of pathologic pain. However, little is known about the structural reorganization of the peripheral astrocytic processes (PAP), the main functional part of the astrocyte, in MDH in neuropathic state. For this, we investigated the structural relationship between PAP and their adjacent presynaptic axon terminals and postsynaptic dendrites in the superficial laminae of the MDH using electron microscopical immunohistochemistry for ezrin, a marker for PAP, and quantitative analysis in a rat model of neuropathic pain following chronic constriction injury of the infraorbital nerve (CCI-ION). We found that, compared to controls, in rats with CCI-ION, (1) the number, % area, surface density, and volume fraction of ezrin-positive (+) PAP, as well as the fraction of synaptic edge apposed by ezrin + PAP and the degree of its coverage of presynaptic axon terminals and postsynaptic dendrites increased significantly, (2) these effects were abolished by administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP). These findings indicate that PAP undergoes structural reorganization around the central synapses of sensory afferents following nerve injury, suggest that it may be mediated by mGluR5, and may represent the structural basis for enhancing astrocyte-neuron interaction in neuropathic pain., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Multiple pregnancy is relatively common in many countries and is associated with various pregnancy complications, including preterm birth, low birth weight, and congenital anomalies. In particular, a poorer prognosis has been reported when congenital anomalies overlap with other pregnancy complications in multiple pregnancy compared with singleton pregnancy., Objective: This study reviews the characteristics of congenital anomalies that occur in multiple gestations as compared with singleton pregnancies., Evidence Acquisition: An extensive manual search of major electronic databases was conducted in June 2023. This literature review provides a comprehensive coverage of the congenital anomalies in multiple pregnancy., Results: Most studies have shown that multiple gestations are associated with an increased risk of congenital anomalies compared with singleton pregnancies. In addition, higher rates of congenital anomalies and concordance have been observed in monozygotic versus dizygotic twins. The effect of assisted reproductive therapies on the risk of congenital anomalies appears to be smaller in multiple gestations than in singleton pregnancies., Conclusions: Multiple pregnancy is significantly associated with an increased risk of congenital anomalies., Relevance: This review provides obstetrical providers with the requisite knowledge to offer appropriate antenatal care and prenatal anomaly screening to patients with multiple pregnancies.

Background and Objectives : Long and ineffective labor causes hardships for mothers and doctors and increases the rate of cesarean sections and medical comorbidities. Several factors contribute to effective and less painful labor, including maternal age, parity, fetal characteristics, and the medications or procedures that obstetricians use for labor. We aimed to study the factors that affect labor duration and identify those that make labor more effective. Materials and Methods : This retrospective study included 141 patients who underwent normal vaginal deliveries at the Daegu Catholic University Medical Center between April 2013 and April 2022. Among the 141 patients, 44 received pethidine intravenously, 88 received oxytocin intravenously, and 64 received epidural anesthesia. The duration of the active phase and second stage of labor were recorded according to the findings of a manual examination of the cervix and continuous external electronic monitoring. We analyzed maternal and neonatal medical records and performed binomial logistic regression to identify the factors associated with a shorter active phase of labor. The clinical outcomes in mothers and neonates were also evaluated. Results : Among the various clinical factors, multiparity (odds ratio of parity 0.325) and the use of pethidine (odds ratio 2.906) were significantly associated with shortening the active phase of labor to less than 60 min. The use of epidural anesthesia or oxytocin was not significantly associated with reducing the active phase of labor. When patients were divided into two groups based on whether a pethidine injection had been used during labor, the duration of the active phase was shorter in the pethidine injection group than in the control group for both nulliparas and multiparas. No significant differences in the duration of the second stage of labor were observed between the pethidine injection and control groups. There were no significant differences in pregnancy outcomes, including the need for mechanical ventilation of neonates, Apgar scores, neonatal intensive care unit admissions, number of precipitous deliveries, maternal adverse side effects of drugs, or duration of maternal hospitalization between the two groups. Conclusions : Pethidine can be safely administered to women during labor to help reduce the duration of the active phase by promoting dilatation of the cervix and preventing complications that may result from prolonged labor. Pethidine may be helpful, especially for those who cannot receive epidural anesthesia or who cannot afford it. However, large-scale randomized controlled studies are required to evaluate the efficacy and safety of this drug during labor. Furthermore, it would be helpful if various studies were conducted depending on the timing of administration and indications for delivery.

Introduction: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. However, little is known about the subpopulations of SGCs that are activated following nerve injury and whether glutamate mechanisms in the SGCs are involved in the pathologic pain., Methods: To address this issue, we used light and electron microscopic immunohistochemistry to examine the change in the glutamate levels in the SGCs and the structural relationship between neighboring neurons in the trigeminal ganglion (TG) in a rat model of craniofacial neuropathic pain, CCI-ION., Results: Administration of ionomycin, ATP and Bz-ATP induced an increase of extracellular glutamate concentration in cultured trigeminal SGCs, indicating a release of glutamate from SGCs. The level of glutamate immunostaining in the SGCs that envelop neurons of all sizes in the TG was significantly higher in rats with CCI-ION than in control rats, suggesting that SGCs enveloping nociceptive as well as non-nociceptive mechanosensitive neurons are activated following nerve injury, and that the glutamate release from SGCs increases in pathologic pain state. Close appositions between substance-P (SP)-immunopositive (+) or calcitonin gene-related peptide (CGRP)+, likely nociceptive neurons, between Piezo1+, likely non-nociceptive, mechanosensitive neurons and SP+ or CGRP+ neurons, and between SGCs of neighboring neurons were frequently observed., Discussion: These findings suggest that glutamate in the trigeminal SGCs that envelop all types of neurons may play a role in the mechanisms of neuropathic pain, possibly via paracrine signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cho, Mah, Youn, Kim, Ko, Bae, Kim and Bae.)

The sustained growth of the market for ophthalmic medical devices has increased the demand for alternatives to animal testing for the evaluation of eye irritation. The International Organization for Standardization has acknowledged the need to develop novel in vitro tests to replace animal testing. Here, we evaluated the applicability of an alternative method based on a human corneal model to test the safety of ophthalmic medical devices. 2-Hydroxyethyl methacrylate (HEMA) and Polymethyl methacrylate (PMMA), which are used to fabricate contact lenses, were used as base materials. These materials were blended with eye irritant and non-irritant chemicals specified in the OECD Test Guideline (TG) 492 and Globally Harmonized System (GHS) classification. Then, three GLP-certified laboratories performed three replicates using the developed method using 3D reconstructed human cornea epithelium, MCTT HCE TM . OECD TG 492 describes the procedure used to evaluate the eye hazard potential of the test chemical based on its ability to induce cytotoxicity in a reconstructed human cornea-like epithelium (RhCE) tissue. Results: The within-laboratory reproducibility (WLR) and between-laboratory reproducibility (BLR) were both 100%. When a polar extraction solvent was used, the sensitivity, specificity, and accuracy were all 100% in each laboratory. When a non-polar extraction solvent was used, the sensitivity was 80%, the specificity was 100%, and the accuracy was 90%. The proposed method exhibited excellent reproducibility and predictive capacity within and between laboratories. Therefore, the proposed method using the MCTT HCE TM model could be used to evaluate eye irritation caused by ophthalmic medical devices.

In this study, ionic conductive hydrogels were prepared with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS). Acrylic acid (AA), acrylamide (AAm), and 2-hydroxyethyl acrylate (HEA) were used as comonomers to complement the adhesion properties and ion conductivity of AMPS hydrogels. Hydrogels were prepared by irradiating a 20 kGy dose of E-beam to the aqueous monomer solution. With the E-beam irradiation, the polymer chain growth and network formation simultaneously proceeded to form a three-dimensional network. The preferred reaction was determined by the type of comonomer, and the structure of the hydrogel was changed accordingly. When AA or AAm was used as a comonomer, polymer growth and crosslinking proceeded together, so a hydrogel with increased peel strength and tensile strength could be prepared. In particular, in the case of AA, it was possible to prepare a hydrogel with improved adhesion without sacrificing ionic conductivity. When the molar ratio of AA to AMPS was 3.18, the 90° peel strength of AMPS hydrogel increased from 171 to 428 g f /25 mm, and ionic conductivity slightly decreased, from 0.93 to 0.84 S/m. By copolymerisation with HEA, polymer growth was preferred compared with chain crosslinking, and a hydrogel with lower peel strength, swelling ratio, and ionic conductivity than the pristine AMPS hydrogel was obtained.

Microvascular function may be modulated by various anesthetics. Desflurane and propofol anesthesia have different effects on microvascular function. However, there are few reports on the effects of sevoflurane and desflurane on microvascular function during cardiac surgery. We compared the effects of sevoflurane and desflurane on microvascular reactivity, as measured by the vascular occlusion tests (VOTs) during off-pump coronary artery bypass (OPCAB) surgery. Patients undergoing OPCAB were eligible for study inclusion. Patients were excluded if they were unsuitable for treatment with volatile agents or the VOT, had renal failure or uncontrolled diabetes, or were pregnant. The enrolled patients were randomized to receive sevoflurane or desflurane during surgery. Tissue oxygen saturation (StO 2 ) dynamics during the VOT were measured at baseline (pre-anesthesia), pre-anastomosis, post-anastomosis of vessel grafts, and at the end of surgery. Macrohemodynamic variables, arterial blood gas parameters, and in-hospital adverse events were also evaluated. A total of 64 patients (32 in each group) were analyzed. StO 2 dynamics did not differ between the groups. Compared to baseline, StO 2 and the rate of recovery following vascular occlusion decreased at the end of surgery in both groups (adjusted p-value, < 0.001), and no group difference was observed. Macrohemodynamic variables, blood gas analysis results, and the rate of postoperative in-hospital adverse events were similar between the groups. Microvascular reactivity, as measured by the VOT during OPCAB, showed no difference between the sevoflurane and desflurane groups. Also, there were no group differences in macrohemodynamics or the rate of postoperative adverse events. TRIAL REGISTRATION : Clinicaltrials.gov, identifier NCT03209193; registered on July 3, 2017., (© 2020. Springer Nature B.V.)

Evidence has mounted that insulin can be synthesized in various brain regions, including the hypothalamus. However, the distribution and functions of insulin-expressing cells in the hypothalamus remain elusive. Herein, we show that in the mouse hypothalamus, the perikarya of insulin-positive neurons are located in the paraventricular nucleus (PVN) and their axons project to the median eminence; these findings define parvocellular neurosecretory PVN insulin neurons. Contrary to corticotropin-releasing hormone expression, insulin expression in the PVN was inhibited by restraint stress (RS) in both adult and young mice. Acute RS-induced inhibition of PVN insulin expression in adult mice decreased both pituitary growth hormone (Gh) mRNA level and serum GH concentration, which were attenuated by overexpression of PVN insulin. Notably, PVN insulin knockdown or chronic RS in young mice hindered normal growth via the downregulation of GH gene expression and secretion, whereas PVN insulin overexpression in young mice prevented chronic RS-induced growth retardation by elevating GH production. Our results suggest that in both normal and stressful conditions, insulin synthesized in the parvocellular PVN neurons plays an important role in the regulation of pituitary GH production and body length, unveiling a physiological function of brain-derived insulin.

Aim: The purpose of this study was to evaluate the prognostic factors of patients with stage IIIC1r cervical cancer who underwent concurrent chemoradiotherapy., Methods: A total of 134 patients treated with chemoradiotherapy for cervical cancer with pelvic and/or paraaortic lymph node metastasis (PALNM) were enrolled in this study. Clinical variables were investigated through review of the patients' medical records., Results: The 5-year overall survival (OS) rate in patients with stage IIICr cervical cancer was 70.5%. Age, PALNM, parametrial invasion, T stage, pelvic side wall invasion, differentiation, lymphovascular space involvement and high squamous cell carcinoma antigen level (>8 ng/mL) were prognostic factors for survival. The 5-year OS rate of patients with stage IIIC1r was 74.5%, and that of stage IIIC2r was 38.1% (P-value = 0.012). The 5-year OS rate of patients with stage IIIC1r with the presence of pelvic side wall invasion was 48.3% and that in its absence was 83.0% (P-value < 0.001). The 5-year OS rate of patients with stage IIIC1r with the presence of parametrial invasion was 68.9% and that in its absence was 82.4% (P-value = 0.031). In multivariable analysis via backward conditional modeling, age, PALNM and pelvic side wall invasion were independent prognostic factors for survival of stage IIICr. Age and pelvic side wall invasion were independent prognostic factors for survival of stage IIIC1r cervical cancer., Conclusion: In stage IIICr cervical cancer, patients with PALNM, and/or pelvic side wall invasion can expect to have a poor prognosis. Particularly, pelvic side wall invasion in stage IIIC1r is an independent prognosis factor., (© 2020 Japan Society of Obstetrics and Gynecology.)

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca 2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

That visceral sensory afferents are functionally distinct from their somatic analogues has been known for a long time but the detailed knowledge of their synaptic connections and neurotransmitters at the first relay nucleus in the spinal cord has been limited. To provide information on these topics, we investigated the synapses and neurotransmitters of identified afferents from the urinary bladder to the superficial laminae of the rat spinal dorsal horn (DH) and the spinal parasympathetic nucleus (SPN) by tracing with horseradish peroxidase, quantitative electron microscopical analysis, and immunogold staining for GABA and glycine. In the DH, most bladder afferent boutons formed synapses with 1-2 postsynaptic dendrites, whereas in the SPN, close to a half of them formed synapses with 3-8 postsynaptic dendrites. The number of postsynaptic dendrites and dendritic spines per bladder afferent bouton, both measures of synaptic divergence and of potential for synaptic plasticity at a single bouton level, were significantly higher in the SPN than in the DH. Bladder afferent boutons frequently received inhibitory axoaxonic synapses from presynaptic endings in the DH but rarely in the SPN. The presynaptic endings were GABA- and/or glycine-immunopositive. The bouton volume, mitochondrial volume, and active zone area, all determinants of synaptic strength, of the bladder afferent boutons were positively correlated with the number of postsynaptic dendrites. These findings suggest that visceral sensory information conveyed via the urinary bladder afferents is processed differently in the DH than in the SPN, and differently from the way somatosensory information is processed in the spinal cord., (© 2019 Wiley Periodicals, Inc.)

Objectives: Chronic obstructive pulmonary disease (COPD) is a fatal disease that shortens one's life expectancy and reduces the quality of life of patients. The current known treatments for COPD can only act to alleviate the symptoms. Recently, stem cells have demonstrated efficacy in various medical areas. The aim of this study was to investigate the possibility of using human Wharton's jelly-derived mesenchymal stem cells (MSC)s for lung recovery in a COPD mouse model., Methods: Human Wharton's jelly was obtained during natural delivery or caesarean section from healthy women. Wharton's jelly-derived MSC was confirmed with expression of CD14, CD34, CD45, CD73, CD90, and CD105 using flow cytometry. Mice model (C57BL/6) of COPD were induced by injecting 10 μL elastase into the trachea and they were divided into three treatment groups (sham, vehicle, stem cell). The sham group was not induced COPD, nor provided any treatment; the vehicle group comprised of COPD-induced mice treated with normal saline; the stem cell group comprised of COPD-induced mice treated with Wharton's jelly-derived MSCs. The vehicle and mesenchymal stem cells (5 × 10 4  cells) were injected in tail vein 7 days following COPD induction. Mice were euthanized 7 days after vehicle and stem cell injection, and pathologic findings were confirmed. Mean Linear Intercept (MLI) was measured after emphysema-induced alveoli were identified., Results: Cell surface markers were positive for CD105, CD90, and CD73 and negative for CD45, CD34, and CD14. Pathological tests showed that COPD-induced mice had significantly increased emphysema volume as compared with that in the sham group. The degree of emphysema in the stem cell group was reduced based on pathologic findings. The mean MLI of the sham group was measured as 38.85 ± 6.45. The mean MLI of the vehicle and stem cell groups were 163.05 ± 48.94 and 123.59 ± 30.53, respectively, and there was a statistically significant difference between the two groups (p = 0.008)., Conclusions: Though the number of mice in the experiment was not large, human Wharton's jelly-derived MSCs showed pulmonary regenerative effects in the COPD mouse model. Although we cannot confirm the effects of Wharton's jelly-derived MSCs in COPD through this experiment, it can be used as a basis for a larger clinical experiment.

The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the Schaffer collateral pathway accounts for the memory acquisition to induce CPP. This astrocytic MOR-mediated LTP induction is dependent on astrocytic glutamate released upon activation of the astrocytic MOR and the consequent activation of the presynaptic mGluR1. The astrocytic MOR-dependent LTP and CPP were recapitulated by a chemogenetic activation of astrocyte-specifically expressed Gi-DREADD hM4Di. Our study reveals that the transduction of inhibitory Gi-signaling into augmented excitatory synaptic transmission through astrocytic glutamate is critical for the acquisition of contextual memory for CPP., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Ruthenium-quercetin conjugated nanoclusters (Ru-QC NCs) were synthesized via a one-pot reflux reaction. As inhalation of heavy metal ions like cobalt can lead to lung cancer, a fluorescent probe was designed for the determination of Co(II) both in aqueous solutions and living cells. The probe consists of hybrid nanoclusters with an average size of 2 nm that were prepared from ruthenium(II) ions and the flavonoid quercetin. These are termed as Ru-QC NCs. They display strong orange-colored emission with a peak at 558 nm under 465-nm excitation. The Ru-QC NCs are cell viable and enable imaging of cells and intracellular fluorometric detection of Co(II). The anticancer properties of Ru-QC NCs were screened by using non-small cell lung cancer (A549) and human dermal fibroblast (HDFa) cell lines. The Ru-QC NCs exert considerable cytotoxicity in A549 cells (at levels of 20-50 μg·mL -1 ), whereas no significant cytotoxicity was observed in case of HDFa cells. The anticancer properties of Ru-QC NCs were screened via MTT assay, live-dead staining, and ROS assay, respectively. Morphological changes of cancer cells were observed using atomic force microscopy. The fluorescent probe can detect Co(II) with a detection limit of 9.28 nM and with a linear response in the 0.03-100 μM concentration range. Graphical abstract Schematic representation of ruthenium-quercetin nanoclusters with potential anticancer properties. They are promising fluorescent probes for intracellular sensing of cobalt (Co 2+ ) and bio-imaging. They exhibited efficient fluorometric detection of Co 2+ with the limit of detection (LOD) of 9.28 nM.

Detailed information about the excitatory and inhibitory synapses on the hypoglossal motoneurons may help understand the neural mechanism for control of the hypoglossal motoneuron excitability and hence the precise and coordinated movements of the tongue during chewing, swallowing and licking. For this, we investigated the distribution of GABA-, glycine (Gly)- and glutamate (Glut)-immunopositive (+) axon terminals on the genioglossal (GG) motoneurons by retrograde tracing, electron microscopic immunohistochemistry, and quantitative analysis. Small GG motoneurons (< 400 μm 2 in cross-sectional area) had fewer primary dendrites, significantly higher nuclear/cytoplasmic ratio, and smaller membrane area covered by synaptic boutons than large GG motoneurons (> 400 μm 2 ). The fraction of inhibitory boutons (GABA + only, Gly + only, and mixed GABA +/Gly + boutons) of all boutons was significantly higher for small GG motoneurons than for large ones, whereas the fraction of Glut + boutons was significantly higher for large GG motoneurons than for small ones. Almost all boutons (> 95%) on both small and large GG motoneurons were GABA + , Gly + or Glut + . The frequency of mixed GABA +/Gly + boutons was the highest among inhibitory boutons types for both small and large GG motoneurons. These findings may elucidate the anatomical substrate for precise regulation of the motoneuron firing required for the fine movements of the tongue, and also suggest that the excitability of small and large GG motoneurons may be regulated differently.

Purpose: The purpose of this study was to evaluate the effectiveness of intrauterine continuous running suture during cesarean section in pregnant women with placenta previa., Methods: We enrolled 277 women and medical records were retrospectively reviewed. Pregnant women were grouped according to uterine bleeding control methods as follows: Group A, using intrauterine continuous running suture and Group B (control group) using figure-of-eight suture., Results: Intrauterine continuous running sutures were used in 104 pregnant women. Mean total blood loss in Group A was significantly less than that in Group B (1332.70 ± 152.92 mL vs 1861.56 ± 157.74 mL, P = 0.029). Mean total transfusion unit of Group A was significantly less than that in Group B (1.74 ± 0.41 vs 3.52 ± 0.75, P = 0.037)., Conclusions: Intrauterine continuous running sutures can significantly reduce postpartum blood loss and transfusion units during cesarean section in pregnant women with placenta previa.

The neurons in the trigeminal mesencephalic nucleus (Vmes) innervate jaw-closing muscle spindles and periodontal ligaments, and play a crucial role in the regulation of jaw movements. Recently, it was shown that many boutons that form synapses on them are immunopositive for glycine (Gly+), suggesting that these neurons receive glycinergic input. Information about the glycine receptors that mediate this input is needed to help understand the role of glycine in controlling Vmes neuron excitability. For this, we investigated the expression of glycine receptor subunit alpha 3 (GlyRα3) and gephyrin in neurons in Vmes and the trigeminal motor nucleus (Vmo), and the Gly+ boutons that contact them by light- and electron-microscopic immunocytochemistry and quantitative ultrastructural analysis. The somata of the Vmes neurons were immunostained for GlyRα3, but not gephyrin, indicating expression of homomeric GlyR. The immunostaining for GlyRα3 was localized away from the synapses in the Vmes neuron somata, in contrast to the Vmo neurons, where the staining for GlyRα3 and gephyrin were localized at the subsynaptic zones in somata and dendrites. Additionally, the ultrastructural determinants of synaptic strength, bouton volume, mitochondrial volume, and active zone area, were significantly smaller in Gly+ boutons on the Vmes neurons than in those on the Vmo neurons. These findings support the notion that the Vmes neurons receive glycinergic input via putative extrasynaptic homomeric glycine receptors, likely mediating a slow, tonic modulation of the Vmes neuron excitability.

Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current ( I h ) on input resistance or I h deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN) have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that I h enhancement apparently diminished the glutamate receptor (GluR) current ( I GluR ) evoked by puff application of glutamate/AMPA and enhanced a transient outward current following I GluR (OT- I GluR ). This suggests that some outward current opposes inward I GluR . The I GluR inhibition displayed a U-shaped voltage-dependence with a minimal inhibition around the resting membrane potential, suggesting that simple shunting effects or deactivation of I h cannot explain the U-shaped voltage-dependence. Confocal imaging of Na + revealed that GluR activation caused an accumulation of Na + in the microvilli, which can cause a negative shift of the reversal potential for I h ( E h ). Taken together, it was suggested that I GluR evoked in MTN neurons is opposed by a transient decrease or increase in standing inward or outward I h , respectively, both of which can be caused by negative shifts of E h , as consistent with the U-shaped voltage-dependence of the I GluR inhibition and the OT- I GluR generation. An electron-microscopic immunohistochemical study revealed the colocalization of HCN channels and glutamatergic synapses in microvilli of MTN neurons, which would provide a morphological basis for the functional interaction between HCN and GluR channels. Mathematical modeling eliminated the possibilities of the involvements of I h deactivation and/or shunting effect and supported the negative shift of E h which causes the U-shaped voltage-dependent inhibition of I GluR .

Recently, we reported that astrocytes in the trigeminal caudal nucleus (Vc) of the brain stem express a purinergic receptor P2X 3 , which is involved in the craniofacial pathologic pain. Although we observed protein expression of P2X 3 receptors (P2X 3 Rs) in the astrocyte of the Vc, it is still unclear that astrocyte has functional P2X 3 Rs in Vc. To address this issue, we recorded asrtocytic P2X 3 Rs by using whole cell voltage-clamp recording in the Vc of the GFAP-GFP mice, which was used as a guide to astrocytes with green fluorescence. While measuring voltage ramp-induced astrocytic membrane current, we found the amplitude of the current was increased when we applied P2-purinoreceptor agonist, α,β-meATP. This increase was blocked by co-application of A317491, P2X 3 R antagonist. These results demonstrate that astrocytes in the Vc express functional P2X 3 Rs, which might be critical in craniofacial pathologic pain.

The purinergic receptor P2X 3 , expressed in the central terminals of primary nociceptive neurons in the brainstem, plays an important role in pathological pain. However, little is known about expression of P2X 3 in the brainstem astrocytes and its involvement in craniofacial pathologic pain. To address this issue, we investigated the expression of P2X 3 in astrocytes in the trigeminal caudal nucleus (Vc) in a rat model of craniofacial neuropathic pain, chronic constriction injury of infraorbital nerve (CCI-ION). We found that 1) P2X 3 -immunoreactivity is observed in the brainstem astrocytes, preferentially in their fine processes, 2) the number of P2X 3 -positive fine astrocytic processes and the density of P2X 3 in these processes were increased significantly in CCI-ION rats, compared to control rats, and 3) administration of MPEP, a specific mGluR5 antagonist, alleviated the mechanical allodynia and abolished the increase in density of P2X 3 in fine astrocytic processes caused by CCI-ION. These findings reveal preferential expression of P2X 3 in the fine astrocytic processes in the brainstem, propose a novel role of P2X 3 in the fine astrocytic process in the mechanism of craniofacial neuropathic pain, and suggest that the expression of astrocytic P2X 3 may be regulated by astrocytic mGluR5.

Increasing evidence shows that the homomeric glycine receptor is expressed in axon terminals and is involved in the presynaptic modulation of transmitter release. However, little is known about the expression of the glycine receptor, implicated in the presynaptic modulation of sensory transmission in the primary somatosensory neurons and their central boutons. To address this, we investigated the expression of glycine receptor subunit alpha 3 (GlyRα3) in the neurons in the trigeminal ganglion and axon terminals in the 1st relay nucleus of the brainstem by light- and electron-microscopic immunohistochemistry. Trigeminal primary sensory neurons were GlyRα3-immunopositive/gephyrin-immunonegative (indicating homomeric GlyR), whereas GlyRα3/gephyrin immunoreactivity (indicating heteromeric GlyR) was observed in dendrites. GlyRα3 immunoreactivity was also found in the central boutons of primary afferents but far from the presynaptic site and in dendrites at subsynaptic sites. Boutons expressing GlyRα3 contained small round vesicles, formed asymmetric synapses with dendrites and were immunoreactive for glutamate. These findings suggest that trigeminal primary afferent boutons receive presynaptic modulation via homomeric, extrasynaptic GlyRα3, and that different subtypes of GlyR may be involved in pre- and postsynaptic inhibition.

Background: A severely deformed vertebra is a matter of concern, particularly when it develops before 24 weeks of gestation, which may lead to compromised pulmonary function and neurological development., Case: A 39-year-old, nulliparous woman presented at 19 weeks of gestation. Her uterus was snowman shaped due to uterine synechiae, and the fetus was confined in the upper section, where amniotic fluid was scanty. The fetal spine was flexed at the upper thoracic level at an angle greater than 90°, with the head flexed and touching the right shoulder throughout pregnancy. Cesarean section was performed at 29+3 weeks of gestation due to preterm labor. A radiograph acquired immediately postpartum showed only a mild degree of spinal flexion, and during the course of hospitalization for respiratory support the infant's spine straightened completely. The infant was discharged without any complications., Conclusion: Here, we report an unusual case of severe fetal spinal deformity observed in early fetal life, and the subsequent positive outcome. We therefore advise caution, following a careful evaluation and consultation, before arriving at a decision of termination.

The rostral nucleus of the solitary tract (rNST) receives gustatory input via chorda tympani (CT) afferents from the anterior two-thirds of the tongue and transmits it to higher brain regions. To help understand how the gustatory information is processed at the 1st relay nucleus of the brain stem, we investigated the central connectivity of the CT afferent terminals in the central subdivision of the rat rNST through retrograde labeling with horseradish peroxidase, immunogold staining for GABA, glycine, and glutamate, and quantitative ultrastructural analysis. Most CT afferents were small myelinated fibers (<5 µm(2) in cross-sectional area) and made simple synaptic arrangements with 1-2 postsynaptic dendrites. It suggests that the gustatory signal is relayed to a specific group of neurons with a small degree of synaptic divergence. The volume of the identified synaptic boutons was positively correlated with their mitochondrial volume and active zone area, and also with the number of their postsynaptic dendrites. One-fourth of the boutons received synapses from GABA-immunopositive presynaptic profiles, 27 % of which were also glycine-immunopositive. These results suggest that the gustatory information mediated by CT afferents to the rNST is processed in a simple and specific manner. They also suggest that the minority of CT afferents are presynaptically modulated by GABA- and/or glycine-mediated mechanism.

The aim of this study was to investigate differences in amino-terminal proB-type natriuretic peptide (NT-proBNP) levels in the cord blood of neonates according to the type of congenital heart disease (CHD) and to evaluate the usefulness of NT-proBNP as a prognostic marker. We included 76 neonates with prenatally diagnosed CHD and 45 controls without CHD. Neonates were classified into five groups based on echocardiographic findings. The levels of NT-proBNP in the cord blood were examined and analyzed according to the neonatal outcomes. The levels of NT-proBNP were significantly elevated in the cord blood of neonates with CHD compared with that in the cord blood of controls. The levels of NT-proBNP in the group with right ventricular outflow tract obstruction without a ventricular septal defect were significantly increased compared to that in the other groups. The neonates that required acute surgical correction had higher levels of NT-proBNP in the cord blood, though they were not statistically significant. Meanwhile, NT-proBNP levels in the cord blood of neonates with functional single ventricle were significantly higher than that in the cord blood of those with functional biventricles. Significant differences in the levels of NT-proBNP between survivors and nonsurvivors were observed within 1 year of birth. In this study, we found that the levels of NT-proBNP in the cord blood of neonates with CHD were higher than the levels in controls. This finding was striking in the group with right ventricular outflow tract obstruction, and it was associated with surgery for functional single ventricle and 1-year survival.

Key Points: We investigated the cellular mechanisms underlying mossy fibre-induced heterosynaptic long-term potentiation of perforant path (PP) inputs to CA3 pyramidal cells. Here we show that this heterosynaptic potentiation is mediated by downregulation of Kv1.2 channels. The downregulation of Kv1.2 preferentially enhanced PP-evoked EPSPs which occur at distal apical dendrites. Such enhancement of PP-EPSPs required activation of dendritic Na(+) channels, and its threshold was lowered by downregulation of Kv1.2. Our results may provide new insights into the long-standing question of how mossy fibre inputs constrain the CA3 network to sparsely represent direct cortical inputs., Abstract: A short high frequency stimulation of mossy fibres (MFs) induces long-term potentiation (LTP) of direct cortical or perforant path (PP) synaptic inputs in hippocampal CA3 pyramidal cells (CA3-PCs). However, the cellular mechanism underlying this heterosynaptic modulation remains elusive. Previously, we reported that repetitive somatic firing at 10 Hz downregulates Kv1.2 in the CA3-PCs. Here, we show that MF inputs induce similar somatic firing and downregulation of Kv1.2 in the CA3-PCs. The effect of Kv1.2 downregulation was specific to PP synaptic inputs that arrive at distal apical dendrites. We found that the somatodendritic expression of Kv1.2 is polarized to distal apical dendrites. Compartmental simulations based on this finding suggested that passive normalization of synaptic inputs and polarized distributions of dendritic ionic channels may facilitate the activation of dendritic Na(+) channels preferentially at distal apical dendrites. Indeed, partial block of dendritic Na(+) channels using 10 nm tetrodotoxin brought back the enhanced PP-evoked excitatory postsynaptic potentials (PP-EPSPs) to the baseline level. These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na(+) channels at distal apical dendrites., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca(2+)-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood., Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity., Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.

Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

Unlabelled: Cellular immunity is pivotal in HIV-1 pathogenesis but is hampered by viral sequence diversity. An approach to minimize this diversity is to focus immunity on conserved proteome sequences; therefore, we selected four relatively conserved regions (Gag amino acids 148 to 214 and 250 to 335, Env amino acids 521 to 606, and Nef amino acids 106 to 148), each created in three mosaics, to provide better coverage of M-group HIV-1 sequences. A conserved-region vaccine (CRV) delivering genes for these four regions as equal mixtures of three mosaics each (each region at a separate injection site) was compared to a whole-protein vaccine (WPV) delivering equimolar amounts of genes for whole Gag, Env, and Nef as clade B consensus sequences (separate injection sites). Three rhesus macaques were vaccinated via three DNA primes and a recombinant adenovirus type 5 boost (weeks 0, 4, 8, and 24, respectively). Although CRV inserts were about one-fifth that of WPV, the CRV generated comparable-magnitude blood CD4+ and CD8+ T lymphocyte responses against Gag, Env, and Nef. WPV responses preferentially targeted proteome areas outside the selected conserved regions in direct proportion to sequence lengths, indicating similar immunogenicities for the conserved regions and the outside regions. The CRV yielded a conserved-region targeting density that was approximately 5-fold higher than that of the WPV. A similar pattern was seen for bronchoalveolar lymphocytes, but with quadruple the magnitudes seen in blood. Overall, these findings demonstrate that the selected conserved regions are highly immunogenic and that anatomically isolated vaccinations with these regions focus immunodominance compared to the case for full-length protein vaccination., Importance: HIV-1 sequence diversity is a major barrier limiting the capability of cellular immunity to contain infection and the ability of vaccines to match circulating viral sequences. To date, vaccines tested in humans have delivered whole proteins or genes for whole proteins, and it is unclear whether including only conserved sequences would yield sufficient cellular immunogenicity. We tested a vaccine delivering genes for four small conserved HIV-1 regions compared to a control vaccine with genes for whole Gag, Env, and Nef. Although the conserved regions ranged from 43 to 86 amino acids and comprised less than one-fifth of the whole Gag/Env/Nef sequence, the vaccines elicited equivalent total magnitudes of both CD4+ and CD8+ T lymphocyte responses. These data demonstrate the immunogenicity of these small conserved regions and the potential for a vaccine to steer immunodominance toward conserved epitopes., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Substance P (SP), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4) are widely used as markers for peripheral neurons with unmyelinated fibers, whereas neurofilament 200 (NF200), and Peripherin are used as markers for neurons with myelinated fibers, and with unmyelinated or small-caliber fibers, respectively. To study the selectivity of these markers for specific neuronal types, we analyzed their expression in neurons in the rat trigeminal ganglion by light- and electron-microscopic immunocytochemistry. Most SP-immunopositive (+), CGRP+, and IB4+ fibers were unmyelinated, but a small fraction (∼5%) were small myelinated fibers (<20 µm(2) in cross-sectional area, equivalent to <5 µm in diameter, Aδ fiber). Similarly, whereas the majority of NF200+ fibers were myelinated, a large fraction (23.9%) were unmyelinated, and whereas the majority of Peripherin+ fibers were unmyelinated and small myelinated, a significant fraction (15.5%) were large myelinated (>20 µm(2) in cross-sectional area, equivalent to >5 µm in diameter, Aβ fiber). Our findings confirm that SP, CGRP, and IB4 can be used as reliable markers for neurons with unmyelinated fibers, and question the suitability of NF200 as a marker for neurons with myelinated fibers, and of Peripherin as a marker for neurons with unmyelinated, or fine-caliber fibers., (© 2014 Wiley Periodicals, Inc.)

In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.

We report a case of a viable abdominal pregnancy with successful outpatient management until fetal lung maturation and planned delivery. Advanced abdominal pregnancy is a very rare extrauterine pregnancy, which results in serious maternal and fetal morbidity. A 28-year-old nullipara was referred from the local clinic to our tertiary center at 18 weeks' gestation. We diagnosed an extrauterine fetus on sonographic examination. The patient had weekly antenatal sonographic examinations. We performed a planned laparotomy at 34 weeks' gestation, and a female baby weighing 2,100 g was delivered. The placenta was completely removed and the uterus was preserved. Both the mother and the baby had no postoperative morbidity., (Copyright © 2012 Wiley Periodicals, Inc.)

Unlike other primary sensory neurons, the neurons in the mesencephalic trigeminal nucleus (Vmes) receive most of their synaptic input onto their somata. Detailed description of the synaptic boutons onto Vmes neurons is crucial for understanding the synaptic input onto these neurons and their role in the motor control of masticatory muscles. For this, we investigated the distribution of γ-aminobutyric acid (GABA)-, glycine-, and glutamate-immunopositive (+) boutons on Vmes neurons and their ultrastructural parameters that relate to transmitter release: Vmes neurons that innervate masseteric muscle spindles were identified by labeling with horseradish peroxidase injected into the muscle, and immunogold staining and quantitative ultrastructural analysis of synapses onto these neurons were performed in adult rats and during postnatal development. The bouton volume, mitochondrial volume, and active zone area of the boutons contacting labeled somata (axosomatic synapses) were similar to those of boutons forming axoaxonic synapses with Vmes neurons but smaller than those of boutons forming axodendritic or axosomatic synapses with most other neurons. GABA+ , glycine+ , and glutamate+ boutons constituted a large majority (83%) of all boutons on labeled somata. A considerable fraction of boutons (28%) was glycine(+) , and all glycine+ boutons were also GABA+ . Bouton size remained unchanged during postnatal development. These findings suggest that the excitability of Vmes neurons is determined to a great extent by GABA, glycine, and glutamate and that the relatively lower synaptic strength of axosomatic synapses may reflect the role of the Vmes neurons in modulating orofacial motor function., (Copyright © 2012 Wiley Periodicals, Inc.)

Inhibitory and excitatory synaptic inputs onto trigeminal motoneurons play an important role in coordinating jaw movements. Previously, we reported that the phenotype of the inhibitory boutons apposing the somata of jaw-closing (JC) motoneurons changes from γ-aminobutyric acid (GABA)-positive (GABA+) to predominantly glycine-positive (Gly+) during development. In the present study, we investigated the development of inhibitory and excitatory boutons apposing antagonistic jaw-opening (JO) motoneurons (anterior digastric motoneurons) at postnatal day 2 (P2), P11, and P31 in the rat. JO motoneurons were retrogradely labeled with horseradish peroxidase. Postembedding immunogold staining with antisera against GABA, Gly, and glutamate (Glut) was performed and followed by quantitative ultrastructural analysis. The size of both small and large JO motoneurons increased during development. The number of excitatory (Glut+) and inhibitory (GABA+, Gly+, and GABA+/Gly+) boutons per JO motoneuron increased significantly from P2 to P11 and then remained unchanged until P31. The time course of inhibitory synapse formation differed between JO and JC motoneurons, whereas that of excitatory synapse formation was similar between the two neuronal populations. The fraction of GABA+ boutons decreased by 86% and the fraction of GABA+/Gly+ boutons increased by 200% from P11 to P31, suggesting a switch from GABA+ to GABA+/Gly+ phenotype. The fraction of Gly+ boutons remained unchanged. These results indicate that inhibitory synapses onto somata of JO motoneurons exhibit a developmental pattern distinct from that of synapses onto JC motoneurons, which may reflect distinctive maturation of oral motor system.

Fetal scalp cysts are rare, and they may be easily misdiagnosed as meningoceles or encephaloceles. A 38-year-old pregnant woman was referred to our hospital for ultrasound examination, which revealed a small cyst above the skull with no defect in the skull. The cyst could not be seen on follow-up ultrasound examinations. After delivery, a three-dimensional CT scan of the head revealed no defect in skull and scalp. Fetal scalp cysts usually require surgical excision after birth, but can regress without any treatment., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: Previous studies have suggested that myelinated axons lose their myelin and become thinner in their peripheral course to the target organ. In this study, we investigated the morphologic changes of pulpal myelinated axons between their root portion (radicular pulp) and their terminal area (peripheral pulp)., Methods: Sections of pulp of the rat upper molar teeth were immunostained for the marker of myelinated axons neurofilament (NF) 200. The proportion of NF200+ myelinated and unmyelinated fibers and their sizes were analyzed by using quantitative electron microscopy., Results: The axon area, myelin thickness, and fraction of NF200+ myelinated axons of all NF200+ axons were significantly lower in peripheral than in radicular pulp. In addition, large unmyelinated axons were frequently observed in peripheral pulp., Conclusions: These results suggest that pulpal innervation originates predominantly from myelinated axons, and the myelinated axons undergo extensive morphologic changes during their course from the radicular to the peripheral pulp., (Copyright © 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Trigeminal primary afferents expressing P2X(3) receptor are involved in the transmission of orofacial nociceptive information. However, little is known about their central projection pattern and ultrastructural features within the trigeminal brainstem sensory nuclei (TBSN). Here we use multiple immunofluorescence and electron microscopy to characterize the P2X(3)-immunopositive (+) neurons in the trigeminal ganglion and describe the distribution and synaptic organization of their central terminals within the rat TBSN, including nuclei principalis (Vp), oralis (Vo), interpolaris (Vi), and caudalis (Vc). In the trigeminal ganglion, P2X(3) immunoreactivity was mainly in small and medium-sized somata, but also frequently in large somata. Although most P2X(3) (+) somata costained for the nonpeptidergic marker IB4, few costained for the peptidergic marker substance P. Most P2X(3) (+) fibers in the sensory root of trigeminal ganglion (92.9%) were unmyelinated, whereas the rest were small myelinated. In the TBSN, P2X(3) immunoreactivity was dispersed in the rostral TBSN but was dense in the superficial laminae of Vc, especially in the inner lamina II. The P2X(3) (+) terminals contained numerous clear, round vesicles and sparse large, dense-core vesicles. Typically, they were presynaptic to one or two dendritic shafts and also frequently postsynaptic to axonal endings, containing pleomorphic vesicles. Such P2X(3) (+) terminals, showing glomerular shape and complex synaptic relationships, and those exhibiting axoaxonic contacts, were more frequently seen in Vp than in any other TBSN. These results suggest that orofacial nociceptive information may be transmitted via P2X(3) (+) afferents to all TBSN and that it may be processed differently in different TBSN., ((c) 2007 Wiley-Liss, Inc.)

We have previously described the distribution pattern of inhibitory synapses on rat jaw-closing (JC) alpha- and gamma-motoneurons. In the present study, we investigated developmental changes in inhibitory synapses on JC motoneurons. We performed a quantitative ultrastructural analysis of putative inhibitory synaptic boutons on JC motoneuron somata by using postembedding immunogold labeling for GABA and glycine. In total, 206, 350, and 497 boutons contacting JC motoneuron somata were analyzed at postnatal days 2 (P2), 11 (P11) and 31 (P31), respectively. The size of the somata increased significantly during postnatal development. The size distribution was bimodal at P31. Mean length of the boutons and percentage of synaptic covering also increased during postnatal development, whereas bouton density did not differ significantly among the three age groups. Synaptic boutons on the somata of JC alpha-motoneurons could be classified into four types: boutons immunoreactive for 1) GABA only, 2) glycine only, 3) both GABA and glycine, and 4) neither GABA nor glycine. There was no developmental change in the proportion of putative inhibitory boutons to the total number of studied boutons. However, the glycine-only boutons increased significantly (15.1% to 27.3%), and the GABA-only boutons decreased significantly (17.7% to 2.6%) during the period from P11 to P31. Our ultrastructural data indicate that the inhibitory synaptic input to JC motoneurons is developmentally regulated and that there is a postnatal switch from GABA to glycine. The postnatal changes revealed in the present study could play an important role in the maturation of the oral motor system., ((c) 2007 Wiley-Liss, Inc.)

The isomerization reaction of 5-vinyl-2-norbornene (VNB) to 5-ethylidene-2-norbornene (ENB) has been performed using a catalytic system consisting of an alkali metal hydride and an amine. Among various amines tested, only aliphatic 1,2-diamines exhibited the activity for the isomerization. The isomerization was also affected by the alkali metal hydride employed. The activity of the alkali metal hydride increased with the increasing size of alkali metal: KH > NaH > LiH. A series of electron paramagnetic resonance (EPR) and UV-vis experiments on the active species suggest that the isomerization of VNB proceeds through a radical mechanism.

Previous studies suggest that sensory information conveyed through trigeminal afferents is more strongly controlled at the level of the first synapse by GABA-mediated presynaptic mechanisms in the trigeminal principal sensory nucleus (Vp) than other sensory nuclei. However, it is unknown if such a mechanism is common to functionally different classes of primary afferent in the same nucleus or across the nuclei. To address these issues, the present study focused on synaptic microcircuits associated with slowly adapting (SA) mechanosensory afferents innervating the periodontal ligaments in the cat Vp and attempted to examine GABA, glycine, and glutamate immunoreactivity in axon terminals involved in the circuits. Afferents were physiologically characterized before injection of horseradish peroxidase (HRP) and preparation for electron microscopy. HRP-labeled afferent boutons were serially sectioned and immunostained with antibodies against GABA, glycine, and glutamate using a postembedding immunogold method. All the afferent boutons examined contacted non-primary dendrites and they were frequently postsynaptic to unlabeled axons (p-endings). Axodendritic and axoaxonic contacts per afferent bouton were 1.3 (46/35) and 2.0 (70/35), respectively. Most p-endings were immunoreactive for GABA (63/70) and also glycine was co-stained in the majority of the p-endings (49/63). Thirty percent of p-endings with the colocalization of GABA and glycine participated in synaptic triads where a p-ending formed a synapse with the same dendrite as the afferent bouton. None of the p-endings was immunoreactive for glutamate. Most afferent boutons were enriched with glutamate but were immunonegative for GABA and glycine. This study provides evidence suggesting that transmission from SA afferents is strongly controlled presynaptically by GABAergic interneurons with colocalized glycine, and that a proportion of these interneurons, involved in synaptic triads, may also have postsynaptic inhibitory actions on target neurons of the SA afferents.