Nitric oxide modulates the firing rate of the rat supraoptic magnocellular neurons

In vitro, nitric oxide (NO) inhibits the firing rate of magnocellular neurosecretory cells (MNCs) of hypothalamic supraoptic and paraventricular nuclei and this effect has been attributed to GABAergic activation. However, little is known about the direct effects of NO in MNCs. We used the patch-clamp technique to verify the effect Of L-arginine, a precursor for NO synthesis, and N-omega-nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of NOS, on spontaneous electrical activity of MNCs after glutamatergic and GABAergic blockade in Wistar rat brain slices. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 mu M) and DL-2-amino-5-phosphonovaleric acid (DL-AP5) (30 mu M) were used to block postsynaptic glutamatergic currents, and picrotoxin (30 mu M) and saclofen (30 mu M) to block ionotropic and metabotropic postsynaptic GABAergic currents. Under these conditions, 500 mu M L-arginine decreased the firing rate from 3.7 +/- 0.6 Hz to 1.3 +/- 0.3 Hz. Conversely, 100 mu M L-NAME increased the firing rate from 3.0 +/- 0.3 Hz to 5.8 +/- 0.4 Hz. All points histogram analysis showed changes in resting potential from -58.1 +/- 0.8 mV to -62.2 +/- 1.1 mV in the presence of L-arginine and from -59.8 +/- 0.7 mV to -56.9 +/- 0.8 mV by L-NAME. Despite the nitrergic modulator effect on firing rate, some MNCs had no significant changes in their resting potential. In those neurons, hyperpolarizing after-potential (HAP) amplitude increased from 12.4 +/- 1.2 mV to 16.8 +/- 0.7 mV by L-arginine, but without significant changes by L-NAME treatment. To our knowledge, this is the first demonstration that NO can inhibit MNCs independent of GABAergic inputs. Further, our results point to HAP as a potential site for nitrergic modulation. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats

Successful reproduction requires that changes in plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oxytocin (OT), estrogen (E-2) and progesterone (P-4) occur together with the display of maternal behaviors. Ovarian steroids and environmental stimuli can affect the dendritic spines in the rat hippocampus. Here, studying Wistar rats, it is described: (a) the sequential and concomitant changes in the hormonal profile of females at postpartum days (PP) 4, 8, 12, 16, 20 and 24, comparing to estrous cycle referential values; (b) the dendritic spine density in the stratum radiatum of CA1 (CA1-SR) Golgi-impregnated neurons in virgin females across the estrous cycle and in multiparous age-matched ones; and (c) the proportion of different types of spines in the CAI-SR of virgin and postpartum females, both in diestrus. Plasma levels of gonadotrophins and ovarian hormones remained low along PP while LH increased and PRL decreased near the end of the lactating period. The lowest dendritic spine density was found in virgin females in estrus when compared to diestrus and proestrus phases or to postpartum females in diestrus (p < 0.03). Other comparisons among groups were not statistically significant (p > 0.4). There were no differences in the proportions of the different spine types in nulliparous and postpartum females (p > 0.2). Results suggest that medium layer CA1-SR spines undergo rapid modifications in Wistar females across the estrous cycle (not quite comparable to Sprague-Dawley data or to hormonal substitutive therapy following ovariectomy), but persistent effects of motherhood on dendritic spine density and morphology were not found in this area. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na(+) channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na(+) imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na(+) clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na(+) gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K(+) currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a `dual` firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials).

Inhibition of spontaneous neurotransmission in the nucleus of solitary tract of the rat by the cannabinoid agonist WIN 55212-2 is not via CB1 or CB2 receptors

Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure. Both CB1 and CB2 cannabinoid receptors have been described in the nucleus tractus solitarius (NTS), which receives direct afferent projections of cardiovascular reflexes. in the present study we evaluated the effects of WIN 55212-2 (WIN), a cannabinoid agonist, on fast neurotransmission in the NTS. We recorded spontaneous post-synaptic currents using the whole-cell configuration in NTS cells in brainstem slices from young rats (25-30 days old). Application of 5 mu M WIN inhibited the frequency of both glutamatergic and GABAergic sPSCs, without affecting their amplitudes. Effects of WIN were not blocked by application of the CB1 antagonist AM251, the CB2 antagonist AM630 or the varmiloid receptor TRPV1 antagonist AMG9810, suggesting that the effect of WIN is via a non-CB1 non-CB2 receptor. Neither the CB1/CB2 agonist HU210 nor the CB1 agonist ACPA affected the frequency of sPSCs. We conclude WIN inhibits the neurotransmission in the NTS of young rats via a receptor distinct from CB1 or CB2. (c) 2008 Elsevier B.V. All rights reserved.

Giant prolapsed submucous leiomyoma: a surgical challenge for gynecologists

We present a case of a 45-year-old woman who presented with irregular vaginal bleeding and menorrhagia for two months, with an episode of massive bleeding initiating 24 hours before with hemodynamic shock. Vaginal inspection showed a soft, rounded, friable mass in vaginal introitus. After hospitalization, blood transfusion and hydration, she was submitted to vaginal myomectomy with the withdrawal of a 12-cm white, solid, huge, pedunculated, leiomyoma; however, hysterectomy was performed due to persistent uterine bleeding. The postoperation period had no complications. Macroscopy showed a retraction of the myoma pedicle. Gynecologists should prioritize clamping of a pedicle before surgery, reducing its size if the tumor is large.

Treatment for low-risk gestational trophoblastic disease: Comparison of single-agent methotrexate, dactinomycin and combination regimens

Objectives. To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. Methods. From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups Results. The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p = 0.2 and p = 0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (P=0.6). Conclusion. Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration. (c) 2007 Elsevier Inc. All rights reserved.

Conductive hearing loss in children with bronchopulmonary dysplasia: A longitudinal follow-up study in children aged between 6 and 24 months

Aims: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD). Study design, subjects and outcome measures: In a longitudinal clinical study. 187 children were evaluated at 6, 9, 12,15 18 and 24 months of age by visual reinforcement audiometry, tympanometry and auditory brain response system. Results: Of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5 min Apgar score. Conclusions: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of Multiple Cranial Burr Hole Surgery on Prevention of Recurrent Ischemic Attacks in Children with Moyamoya Disease

Moyamoya disease (MMD) is an uncommon cerebrovascular disorder characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. Direct and indirect bypass techniques have been devised with the aim of promoting neoangiogenesis. The current study aimed to investigate the role of multiple cranial burr hole (MCBH) operations in the prevention of cerebral ischemic attacks in children with MMD. Seven children suffering from progressive MMD were submitted to the MCBH and arachnoid opening technique. Ten to 20 burr holes were drilled in the fronto-temporo-parieto-occipital area of each hemisphere in each patient, depending on the site and extent of the disease. All patients were evaluated pre- and postoperatively by means of Barthel index (BI), CT, MR, angio-MR, and angiography. Patients had no recurrence of ischemic attacks postoperatively. Neoangiogenesis was observed in both hemispheres. One patient developed a persistent subdural collection after surgery, thus requiring placement of a subdural-peritoneal shunt. Postoperative BI was statistically significantly improved (P = 0.02). This report suggests that MCBH for revascularization in MMD is a simple procedure with a relatively low risk of complications and effective for preventing cerebral ischemic attacks in children. In addition, MCBH may be placed as an adjunct to other treatments for MMD.

Precise Temporal Regulation of roughest is Required for Correct Salivary Gland Autophagic Cell Death in Drosophila

The Drosophila roughest (rst) locus encodes an immunoglobulin superfamily transmembrane glycoprotein implicated in a variety of embryonic and postembryonic developmental processes. Here we demonstrate a previously unnoticed role for this gene in the autophagic elimination of larval salivary glands during early pupal stages by showing that overexpression of the Rst protein ectodomain in early pupa leads to persistence of salivary glands up to at least 12 hours after head eversion, although with variable penetrance. The same phenotype is observed in individuals carrying the dominant regulatory allele rst(D), but not in loss of function alleles. Analysis of persistent glands at the ultrastructural level showed that programmed cell death starts at the right time but is arrested at an early stage of the process. Finally we describe the expression pattern and intracellular distribution of Rst in wild type and rstD mutants, showing that its downregulation in salivary glands at the beginning of pupal stage is an important factor in the correct implementation of the autophagic program of this tissue in space and time. genesis 47:492-504, 2009. (C) 2009 Wiley-Liss, Inc.

Hydrocephalus in posterior fossa tumors in children. Are there factors that determine a need for permanent cerebrospinal fluid diversion?

We searched for factors that could predispose towards persistent hydrocephalus in children with posterior fossa (PF) tumors in order to determine the need for permanent cerebrospinal fluid (CSF) diversion. The clinical records of 64 children who underwent surgery for PF tumors in the Pediatric Neurosurgery division of the Hospital of Clinics, Ribeirao Preto, Brazil, from 1990 to 2006, were retrospectively reviewed. The patients` ages ranged from 3 months to 18 years. The factors evaluated included age at surgery, severity of hydrocephalus (ventricular index), tumor location, size of the tumor, extent of tumor resection, and histology. Ventricular index, measured from the initial neuroradiological image, age at surgery, and location of the tumor were significantly associated with definitive postoperative CSF diversion (shunt or endoscopic third ventriculostomy), which was necessary for 34% of the patients. Young children with severe preoperative hydrocephalus and a midline tumor should be considered at risk when preoperative treatment decisions are made.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Results: Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. Conclusions: In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

FURTHER INSIGHTS TOWARD VITAMIN C DETERMINATION AND STABILITY. PROPOSAL OF A NEW QUANTIFICATION METHOD

This work aimed at an evaluation of the classical iodine method for quantification of vitamin C (L-ascorbic acid) in fruit juices, as well as at a search into the stability of this so popular vitamin under different conditions of pH, temperature and light exposition, in addition to a proposal of a new quantification method. Our results point to the persistent reversibility of the blue color of the starch-triiodide complex at the end point when using the classical iodine titration, and the overestimation of the true vitamin concentration in fruit juices. A new quantification method is proposed in order to overcome this problem. Surprising conclusions were obtained regarding the controversial stability of L-ascorbic acid toward atmospheric oxygen, at low pH, even in fruit juice and at room temperature, showing that the major problem concerned with aging of fruit juices is proliferation of microorganisms rather than expontaneous oxidation of L-ascorbic acid.

Cyclic Fatigue Resistance of Rotary Nickel-Titanium Instruments Submitted to Nitrogen Ion Implantation

Introduction: The aim of this study was to assess cyclic fatigue resistance in rotary nickel-titanium instruments submitted to nitrogen ion implantation by using a custom-made cyclic fatigue testing apparatus. Methods: Thirty K3 files, size #25, taper 0.04, were divided into 3 experimental groups as follows: group A, 12 files exposed to nitrogen ion implantation at a dose of 2.5 x 10(17) ions/cm(2), accelerating voltage of 200 kV, currents of 1 mu A/cm(2), 130 degrees C temperature, and vacuum conditions of 10 x 10(-6) torr for 6 hours; group B, 12 nonimplanted files; and group C, 6 files submitted to thermal annealing for 6 hours at 130 degrees C. One extra file was used for process control. All files were submitted to a cyclic fatigue test that was performed with an apparatus that allowed the instruments to rotate freely, simulating rotary instrumentation of a curved canal (40-degree, 5-mm radius curve). An electric motor handpiece was used with a contra-angle of 16:1 at an operating speed of 300 rpm and a torque of 2 N-cm. Time to failure was recorded with a stopwatch in seconds and subsequently converted to number of cycles to fracture. Data were analyzed with the Student t test (P < .05). Results: Ion-implanted instruments reached significantly higher cycle numbers before fracture (mean, 510 cycles) when compared with annealed (mean, 428 cycles) and nonimplanted files (mean, 381 cycles). Conclusions: Our results showed that nitrogen ion implantation improves cyclic fatigue resistance in rotary nickel-titanium instruments. Industrial implementation. of this surface modification technique would produce rotary nickel-titanium instruments with a longer working life. (J Endod 2010;36:1183-1186)

Nasopharyngeal angiofibroma. surgical approach using a transoral Le Fort I osteotomy following embolization: a case report

Nasopharyngeal angiofibroma (NA) is a rare vascular benign nonencapsulated neoplasm, characterized by local aggressiveness and destructive potential, typically diagnosed in adolescent males. We report a case of NA affecting a 15-year-old male that presented with a persistent nasal obstruction and epistaxis with 1 year of evolution. Clinical and radiological patterns pointed out a differential diagnosis of NA. Arteriography demonstrates the vascular support of the tumor and evinces the embolization of the internal maxillary artery. The surgical approach was procedure by Le Fort I osteotomy exposing the tumor and promoting easy access for posterior removal. The surgery was carried out without hemorrhagic problems. The maxilla was fixed in the original position with 4 L-shape plaques. Histopathological findings supported the diagnosis of NA. The patient presented after 8 months of postoperative follow-up, without clinical signs of recurrence or residual tumor and without palatal or maxillary teeth paresthesia.

Long-term effects of pharyngeal flaps on the upper airways of subjects with velopharyngeal insufficiency

Objectives: To investigate the long-term effects of pharyngeal flap surgery (PFS) on nasal and nasopharyngeal dimensions of patients with velopharyngeal insufficiency (VPI) and to correlate the findings with the onset of respiratory complaints after surgery. Design/Participants: Prospective study in 58 nonsyndromic patients with repaired cleft palate and VPI, evaluated 2 days before and 5 months (POST1) and 1 year (POST2) after PFS, on average. Patients were divided into two groups: one consisting of patients with postoperative respiratory complaints (RC group) and the other without complaints (NRC group). Interventions: Superiorly based PFS. Main Outcome Measures: Respiratory complaints (self reports of mouth breathing, snoring, and other sleep obstructive events) assessed at POST1 and POST2, and minimum nasal (NCSA) and nasopharyngeal (NPA) cross-sectional areas assessed by rhinomanometry at POST2. Results: Respiratory complaints were reported by 55% and 36% of the patients evaluated at POST1 and POST2, respectively. Posterior rhinomanometry showed a significant postoperative reduction of mean NCSA in the RC and NRC groups (p < .05), to subnormal levels in some of them. The decrease was more pronounced in the RC group. No significant changes in NCSA were observed by anterior rhinomanometry. Similar results were obtained when NPA was assessed by modified anterior rhinomanometry. Conclusion: In the long-term, PFS yielded a significant reduction in upper airways dimensions beyond what should be expected and associated with persistent respiratory complaints in some cases.