Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood

Background: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD. (C) 2011 Elsevier B.V. All rights reserved.

Anxiolytic-like effect of oxytocin in the simulated public speaking test

Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test. Assessments were made across time during the experimental session: (1) baseline (-30 min); (2) pre-test (-15 min); (3) anticipation of the speech (50 min); (4) during the speech (1:03 h), post-test time 1 (1:26 h), and post-test time 2 (1:46 h). Subjective states were evaluated by self-assessment scales. Cortisol serum and plasma adrenocorticotropic hormone (ACTH) were measured. Additionally, heart rate, blood pressure, skin conductance, and the number of spontaneous fluctuations in skin conductance were measured. Compared with placebo, OT reduced the Visual Analogue Mood Scale (VAMS) anxiety index during the pre-test phase only, while increasing sedation at the pre-test, anticipation, and speech phases. OT also lowered the skin conductance level at the pre-test, anticipation, speech, and post-test 2 phases. Other parameters evaluated were not significantly affected by OT. The present results show that OT reduces anticipatory anxiety, but does not affect public speaking fear, suggesting that this hormone has anxiolytic properties.

Approach to the Patient with Persistent Hyperprolactinemia and Negative Sellar Imaging

Hyperprolactinemia is a common cause of menstrual disturbances affecting young women. There is a diversity of causes, from physiological, such as pregnancy, to pharmacological and pathological, such as hypothyroidism. Renal and hepatic failure, intercostal nerve stimulation by trauma or surgery, prolactinomas, other tumors in the hypothalamus-pituitary region, as well as macroprolactinemia can also be considered. Identifying the correct cause is important to establish the correct treatment. Should all these causes be ruled out and pituitary imaging revealed as negative, idiopathic hyperprolactinemia is therefore diagnosed. In symptomatic patients, treatment with dopaminergic agonists is indicated. As for the asymptomatic hyperprolactinemic individuals, macroprolactinemia should be screened, and once it is detected, there is no need for pituitary imaging study or for dopaminergic agonist use. (J Clin Endocrinol Metab 97: 2211-2216, 2012)

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Cortisol Profile and Clinical Evaluation of Canine Neonates Exposed Antenatally to Maternal Corticosteroid Treatment

Contents The effects of glucocorticoids on both foetal canine lung and endogenous serum cortisol concentration have not been clearly delineated. Therefore, we aimed to investigate whether maternal corticosteroid treatment can alter maternal and neonatal cortisol profile and improve neonatal vitality. We allocated six bitches of different breeds and their neonates into two groups: control group (CONT) maternal administration of saline solution at 55days post-ovulation (n=3); and betamethasone group (BETA) administration of a single dose of 0.5mg/kg betamethasone (Celestone Soluspan(R)) at 55days post-ovulation (n=3). Caesarean sections were scheduled for day 63 after ovulation. However, BETA group dams showed precocious signs of labour, and c-sections were performed at 58days post-ovulation. Maternal and neonatal evaluations were performed periodically between betamethasone administration and birth, respectively. Neonates from both groups presented unsatisfactory (<5) Apgar score at birth. However, in spite of an earlier improvement on vitality found on CONT group and the premature delivery on BETA group, both groups showed acceptable Apgar score 120min after birth. Neonatal cortisol concentrations were higher on CONT group compared to BETA group at birth. In addition, a gradual decrease on maternal cortisol concentrations was observed in the BETA group from treatment until parturition. These findings suggest that despite the down-regulation on the hypothalamic-pituitary-adrenal axis and the induction of premature delivery, betamethasone treatment was able to provide similar vitality when compared to the untreated neonates born at term.

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel

Cardiovascular effects of the microinjection of L-proline into the third ventricle or the paraventricular nucleus of the hypothalamus in unanesthetized rats

We investigated the cardiovascular effects of the microinjection of L-proline (L-Pro) into the third ventricle (3V) and its peripheral mechanisms. Different doses of L-Pro into the 3V caused dose-related pressor and bradycardiac responses. The pressor response to L-Pro injected into the 3V was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), thus excluding any significant involvement of the sympathetic nervous system. Because the response to the microinjection of L-Pro into the 3V was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 mu g/kg), it is suggested that these cardiovascular responses are mediated by a vasopressin release. The pressor response to the microinjection of L-Pro into the 3V was found to be mediated by circulating vasopressin, so, given that the paraventricular nucleus of the hypothalamus (PVN) is readily accessible from the 3V, we investigated whether the PVN could be a site of action for the L-Pro microinjected in the 3V. The microinjection of L-Pro (0.033 mu moles/0.1 mu l) into the PVN caused cardiovascular responses similar to those of injection of the 3V and were also shown to be mediated by vasopressin release. In conclusion, these results show that the microinjection of L-Pro into the 3V causes pressor and bradycardiac responses that could involve stimulation of the magnocellular cells of the PVN and release of vasopressin into the systemic circulation. Also, because the microinjection of L-Pro into the PVN caused a pressor response, this is the first evidence of cardiovascular effects caused by its injection in a supramedullary structure. (c) 2012 Wiley Periodicals, Inc.

Fast detection of the magnetic easy axis on steel sheet using the continuous rotational Barkhausen method

The magnetic behaviour of most commercial ferromagnetic steels is usually anisotropic presenting a magnetic easy axis. Changes in the direction of this axis can be related to mechanical changes and anomalies that occur in the fabrication process. The present work describes a method that uses a device with permanent magnets to create a precise rotational magnetic field. The device measures continuous Magnetic Barkhausen Noise signals related to the angle of magnetization, in order to determine the direction of the macroscopic magnetic easy axis. It also offers the possibility of obtaining real time parameters that quantify the magnetic anisotropy of the sample. (C) 2011 Elsevier Ltd. All rights reserved.

Feasibility of Intralaminar, Lateral Mass, or Pedicle Axis Vertebra Screws in Children Under 10 Years of Age: A Tomographic Study

BACKGROUND: There are several techniques for screw insertion in upper cervical spine surgery, and the use of the 3.5-mm screw is usually the standard. However, there is no consensus regarding the feasibility of using these screws in the pediatric population. OBJECTIVE: To determine the measurement of the lamina angle, lamina and pedicle length and thickness, and lateral mass length of the topographic axial view of the axis vertebra of 2- to 10-year-old children to guide the use of surgical screws. METHODS: Seventy-five computed tomography scans from 24- to 120-month-old patients were studied. Measurements were taken in an axial view of C2 and correlated with 2 age groups and both sexes. Statistical analysis was performed with the Student t test. RESULTS: In the 24- to 48-month age group, only 5.5% of the lamina and 8.3% of the pedicles had thicknesses < 3.5 mm. In the 49- to 120-month age group, there were no lamina thickness values < 3.5 mm, and 1.2% of pedicle thicknesses were < 3.5 mm. Both age groups had no lamina and pedicle lengths < 12 mm and no lateral mass lengths > 12 mm. CONCLUSION: In the majority of cases, the use of 3.5-mm lamina and pedicle screws in children is feasible. A base value of 45 degrees for the spinolaminar angle can be adopted as a reference for insertion of screws in the C2 lamina. This information can be particularly useful for decision making during preoperative planning for C1-C2 or craniocervical arthrodesis in children.

TOMOGRAPHIC ANALYSIS OF ANATOMICAL PARAMETERS OF THE AXIS IN CHILDREN

Objective: To carry out an anatomical study of the axis with the use of computed tomography (CT) in children aged from two to ten years, measuring the lamina angle, lamina and pedicle length and thickness, and lateral mass length. Methods: Sixty-four CTs were studied from patients aged 24 to 120 months old, of both sexes and without any cervical anomaly. The measurements obtained were correlated with the data on age and sex of the patients. Statistical analysis was performed using the Students "t" tests. Results: We found that within the age range 24-48 months, 5.5% of the lamina and 8.3% of the pedicles had thicknesses of less than 3.5mm, which is the minimum thickness needed for insertion of the screw. Between 49 and 120 months, there were no lamina thicknesses of less than 3.5mm, and 1.2% of the pedicle thicknesses were less than 3.5mm values. Neither of the age groups had any lamina and pedicle lengths of less than 12mm, or lateral mass lengths greater than 12mm. Conclusion: The analysis of the data obtained demonstrates that most of the time, is possible to use a 3.5mm pedicle screw in the laminas and pedicles of the axis in children. Level of Evidence: II, Development of diagnostic criteria in consecutive patients.

TRAUMATIC SPONDYLOLISTHESIS OF THE AXIS: EPIDEMIOLOGY, MANAGEMENT AND OUTCOME

Objective: To evaluate cases of traumatic spondylolisthesis of the axis and describe them in relation to epidemiology, classification, neurological deficit, healing time and treatment method. Method: A retrospective analysis of the medical records of patients treated between 2002 and 2010 at IOT-FMUSP. Inclusion criteria: pars interarticularis fracture of C2. Results: 68% were male patients, with a mean age of 39.1 years. We used the classification by Effendi, modified by Levine-Edwards. Type I fractures were observed in five patients (31.2%) and type II in eight patients (50%). Only three patients (18%) had type IIa fracture. There were no cases of type III. Mechanism: Eight car accidents and four falls. Other mechanisms: being run over, and diving accidents. Treatment with halo traction was used in eleven patients, using minerva cast and halo-cast. Healing time: 3.6 months. Follow-up time: 9.6 months. Discussion: In general, hangman fracture has a good prognosis, which is confirmed by our results. There was no need for surgery in any of the cases. The incidence of neurological deficit is low. No patient had unstable fracture (type III). Conclusion: This paper suggests that traumatic spondylolisthesis of the axis continues to be an injury that is successfully treated by conservative treatment in most cases. Level of Evidence IV, Case series.

Glutamatergic neurotransmission in the hypothalamus PVN on heart rate variability in exercise trained rats

The paraventricular nucleus of hypothalamus (PVN) is a well known site of integration for autonomic and cardiovascular responses, and the glutamate neurotransmitter plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after ionotropic glutamate receptor inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After exercise training protocol, adult male Wistar rats, instrumented with guide cannulae to PVN and artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, physical training induced a resting bradycardia (S: 379 +/- 3, ST: 349 +/- 2 bpm, P<0.05) and promoted adaptations in HRV characterized by an increase of HF in normalized values and a decrease of LF in absolute and normalized units compared with the sedentary group. Microinjection of kynurenic acid (KYNA) in the PVN of sedentary and trained rats promoted decreases in MAP and HR, but the decrease in HR was smaller in the trained animals (Delta HRS: -48 +/- 7, ST: -28 +/- 4 bpm, P<0.05). Furthermore, the differences in baseline parameters of pulse interval, found between sedentary and trained animals, disappeared after KYNA microinjection in the PVN. Our data suggest that the cardiovascular and autonomic adaptations to the heart induced by exercise training may involve glutamatergic mechanisms in the PVN. (C) 2012 Elsevier B.V. All rights reserved.

Macrophage Dectin-1 Expression Is Controlled by Leukotriene B-4 via a GM-CSF/PU.1 Axis

Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B-4 (LTB4). The influence of G protein-coupled receptor ligands such as LTB4 on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB4 signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB4 production and signaling through its high-affinity G protein-coupled receptor leukotriene B4 receptor 1 (BLT1) direct dectin-1-dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wildtype counterparts. LTB4 increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB4-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB4 effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF-/- macrophages. Our results identify LTB4-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses. The Journal of Immunology, 2012, 189: 906-915.

SAGE analysis highlights the putative role of underexpression of ribosomal proteins in GH-secreting pituitary adenomas

Background: Although the molecular pathogenesis of pituitary adenomas has been assessed by several different techniques, it still remains partially unclear. Ribosomal proteins (RPs) have been recently related to human tumorigenesis, but they have not yet been evaluated in pituitary tumorigenesis. Objective: The aim of this study was to introduce serial analysis of gene expression (SAGE), a high-throughput method, in pituitary research in order to compare differential gene expression. Methods: Two SAGE cDNA libraries were constructed, one using a pool of mRNA obtained from five GH-secreting pituitary tumors and another from three normal pituitaries. Genes differentially expressed between the libraries were further validated by real-time PCR in 22 GH-secreting pituitary tumors and in 15 normal pituitaries. Results: Computer-generated genomic analysis tools identified 13 722 and 14 993 exclusive genes in normal and adenoma libraries respectively. Both shared 6497 genes, 2188 were underexpressed and 4309 overexpressed in tumoral library. In adenoma library, 33 genes encoding RPs were underexpressed. Among these, RPSA, RPS3, RPS14, and RPS29 were validated by real-time PCR. Conclusion: We report the first SAGE library from normal pituitary tissue and GH-secreting pituitary tumor, which provide quantitative assessment of cellular transcriptome. We also validated some downregulated genes encoding RPs. Altogether, the present data suggest that the underexpression of the studied RP genes possibly collaborates directly or indirectly with other genes to modify cell cycle arrest, DNA repair, and apoptosis, leading to an environment that might have a putative role in the tumorigenesis, introducing new perspectives for further studies on molecular genesis of somatotrophinomas.

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.