Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression

The effects of microinjection of the nitric oxide (NO) precursor L-arginine (L-Arg), the NO synthase (NOS) inhibitors N-methyl-L-arginine (L-NAME) and 7-nitroindazole (7-NI), and the cyclic guanosine 3`,5`-monophosphate (cGMP) analog 8-Br-cGMP into the dorsal raphe nucleus (DRN) were assessed in rats using the elevated plus maze (EPM) and the forced swim test (FST). L-Arg (100 and 200 nmol) produced an anxiolytic-like effect in the EPM. 8-Br-cGMP (25 and 50 nmol) dose-dependently increased locomotor activity. In the FST, antidepressant-like effects were produced by L-Arg (50 and 100 nmol) and 8-Br-cGMP (12.5 and 25 nmol). Dual effects were observed with NOS inhibitors L-NAME and 7-NI in both the EPM and FST. While low doses of L-NAME (25 nmol) or 7-NI (1 nmol) induced a selective increase in EPM open arm exploration and a decrease in immobility time in the FST, high doses (L-NAME 400 nmol, 7-NI 10 nmol) decreased locomotor activity. These results show that interference with NO-mediated neurotransmission in the DRN induced significant and complex motor and emotional effects. Further studies are needed to elucidate the mechanisms involved in these effects. (C) 2007 Elsevier Inc. All rights reserved.

An anti-inflammatory lectin from Luetzelburgia auriculata seeds inhibits adhesion and rolling of leukocytes and modulates histamine and PGE2 action in acute inflammation models

To study and characterize the in vivo effect of the lectin from Luetzelburgia auriculata seed on acute inflammation models. The lectin was purified from the crude saline extract by affinity chromatography on a guar-gum matrix. Native, heat-treated, and digested lectin was evaluated for anti-inflammatory activity by using peritonitis and paw edema models. The anti-inflammatory activity was characterized by intravital microscopy, nitric oxide production, and myeloperoxidase activity. The lectin exhibited anti-inflammatory activity (2 mg/kg) on both models, reducing local myeloperoxidase activity. Galactose or heat treatment (100A degrees C, 10 min) reduced anti-inflammatory action. Anti-inflammation involves the inhibition of adhesion and rolling of leukocytes along with augmentation of nitric oxide in serum. The lectin inhibited the edematogenic effect of histamine and prostaglandins (PGE2) but did not alter the chemoattractant effect of IL-8. The results indicate that this lectin is a potent anti-inflammatory molecule. Its effects engage diverse modulatory events.

Models for genetic evaluation of Nelore cattle mature body weight

Records of 18,770 Nelore animals, born from 1975 to 2002, in 8 herds participating in the Nelore Cattle Breeding Program, were analyzed to estimate genetic parameters for mature BW. The mature BW were analyzed as a single BW taken closest to 4.5 yr of age for each cow in the data file, considering BW starting from 2 (W2Y_S), 3 (W3Y_S), or 4 (W4Y_S) yr of age or as repeated records, including all BW starting from 2 (W2Y_R), 3 (W3Y_R), or 4 (W4Y_R) yr of age. The variance components were estimated by restricted maximum likelihood, fitting univariate and bivariate animal models, including weaning weight. The heritability estimates were 0.29, 0.34, 0.36, 0.41, 0.44, and 0.46 for W2Y_S, W3Y_S, W4Y_S, W2Y_R, W3Y_R, and W4Y_R, respectively. The repeatability estimates for W2Y_R, W3Y_R, and W4Y_R were 0.59, 0.64, and 0.72, respectively. Larger accuracy values associated with the EBV were obtained in the repeated records models. The results indicated the bivariate repeated records model as the most appropriate for analyzing mature BW.

Neurobiology of panic disorder: From animal models to brain neuroimaging

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG). Stressing the difference between these emotions, neuroendocrinological results indicate that the hypothalamic-pituitary-adrenal axis is activated by anticipatory anxiety, but not by panic attack nor by electrical stimulation of the rat PAG. Functional neuroimaging has shown activation of the insula and upper brain stem (including PAG), as well as deactivation of the anterior cingulated cortex (ACC) during experimental panic attacks. Voxel-based morphometric analysis of brain magnetic resonance images has shown a grey matter volume increase in the insula and upper brain stem, and a decrease in the ACC of panic patients at rest, as compared to healthy controls. The insula and the ACC detect interoceptive stimuli, which are overestimated by panic patients. It is suggested that these brain areas and the PAG are involved in the pathophysiology of panic disorder. (C) 2008 Elsevier Ltd. All rights reserved.

CHARACTERIZATION OF Kiss1 NEURONS USING TRANSGENIC MOUSE MODELS

Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or beta-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Me lanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Impact of implementing an exclusively dedicated respiratory isolation room in a Brazilian tertiary emergency department

Background Occupational risk due to airborne disease challenges healthcare institutions. Environmental measures are effective but their cost-effectiveness is still debatable and most of the capacity planning is based on occupational rates. Better indices to plan and evaluate capacity are needed. Goal To evaluate the impact of installing an exclusively dedicated respiratory isolation room (EDRIR) in a tertiary emergency department (ED) determined by a time-to-reach-facility method. Methods A group of patients in need of respiratory isolation were first identified-group I (2004; 29 patients; 44.1 +/- 3.4 years) and the occupational rate and time intervals (arrival to diagnosis, diagnosis to respiratory isolation indication and indication to effective isolation) were determined and it was estimated that adding an EDRIR would have a significant impact over the time to isolation. After implementing the EDRIR, a second group of patients was gathered in the same period of the year-group II (2007; 50 patients; 43.4 +/- 1.8 years) and demographic and functional parameters were recorded to evaluate time to isolation. Cox proportional hazard models adjusted for age, gender and inhospital respiratory isolation room availability were obtained. Results Implementing an EDRIR decreased the time from arrival to indication of respiratory isolation (27.5 +/- 9.3 X 3.7 +/- 2.0; p = 0.0180) and from indication to effective respiratory isolation (13.3 +/- 3.0 X 2.94 +/- 1.06; p = 0.003) but not the respiratory isolation duration and total hospital stay. The impact on crude isolation rates was very significant (8.9 X 75.4/100.000 patients; p < 0.001). The HR for effective respiratory isolation was 26.8 (95% CI 7.42 to 96.9) p < 0.001 greater for 2007. Conclusion Implementing an EDRIR in a tertiary ED significantly reduced the time to respiratory isolation.

Maned wolf survival rate in central Brazil

Although many carnivores are of conservation concern, most are poorly studied. The maned wolf Chrysocyon brachyurus Illiger, 1811 is the largest South American canid with a broad distribution; however, the largest portion of its range is in the Brazilian Cerrado savannah, where due to intensive agricultural expansion, it is threatened by habitat loss. Maned wolf population trends are virtually unknown. We analyzed radio telemetry data from a 13-year study in Emas National Park, central Brazil, with Burnham`s live recapture/dead recovery models in the program MARK to obtain the first analytically sound estimate of the apparent maned wolf survival rate. We constructed 16 candidate models including variation in survival rate and resighting probability associated with an individual`s sex or age and year of study. Apparent adult survival rate throughout the study ranged from 0.28 (se=0.08) to 0.97 (se=0.06). There was no evidence for sex specificity but strong support for time variation. Model weights supported an age effect and the subadult survival rate was 0.63 (se=0.15). Results indicate similar life patterns for male and female maned wolves and similar mortality risks for adults and subadults in the study area. The observed temporal fluctuations of adult survival rate are important for population dynamics as they decrease average population growth rates. Population dynamics are central for conservation planning and our results are an important step towards a better understanding of the maned wolf`s ecology.

The neuroprotective effect of dental pulp cells in models of Alzheimer`s and Parkinson`s disease

Aim of the present study was to investigate the neuroprotective effect of dental pulp cells (DPCs) in in vitro models of Alzheimer and Parkinson disease. Primary cultures of hippocampal and ventral mesencephalic neurons were treated for 24 h with amyloid beta (A beta(1-42)) peptide 1-42 and 6-OHDA, respectively. DPCs isolated from adult rat incisors were previously cultured in tissue culture inserts and added to the neuron cultures 2 days prior to neurotoxin treatment. Cell viability was assessed by the MTT assay. The co-culture with DPCs significantly attenuated 6-OHDA and A beta(1-42)-induced toxicity in primary cultures of mesencephalic and hippocampal neurons, and lead to an increase in neuronal viability in untreated cultures, suggesting a neurotrophic effect in both models. Furthermore, human dental pulp cells expressed a neuronal phenotype and produced the neurotrophic factors NGF, GDNF, BDNF, and BMP2 shown by microarray screening and antibody staining for the representative proteins. DPCs protected primary neurons in in vitro models of Alzheimer`s and Parkinson`s disease and can be viewed as possible candidates for studies on cell-based therapy.

Precise Insertion of Orthodontic Miniscrews with a Stereolithographic Surgical Guide Based on Cone Beam Computed Tomography Data: A Pilot Study

Purpose: Orthodontic miniscrews are commonly used to achieve absolute anchorage during tooth movement. One of the most frequent complications is screw loss as a result of root contact. Increased precision during the process of miniscrew insertion would help prevent screw loss and potential root damage, improving treatment outcomes. Stereo lithographic surgical guides have been commonly used for prosthetic implants to increase the precision of insertion. The objective of this paper was to describe the use of a stereolithographic surgical guide suitable for one-component orthodontic miniscrews based on cone beam computed tomography (CBCT) data and to evaluate implant placement accuracy. Materials and Methods: Acrylic splints were adapted to the dental arches of four patients, and six radiopaque reference points were filled with gutta-percha. The patients were submitted to CBCT while they wore the occlusal splint. Another series of images was captured with the splint alone. After superimposition and segmentation, miniscrew insertion was simulated using planning software that allowed the user to check the implant position in all planes and in three dimensions. In a rapid-prototyping machine, a stereolithographic guide was fabricated with metallic sleeves located at the insertion points to allow for three-dimensional control of the pilot bur. The surgical guide was worn during surgery. After implant insertion, each patient was submitted to CBCT a second time to verify the implant position and the accuracy of the placement of the miniscrews. Results: The average differences between the planned and inserted positions for the ten miniscrews were 0.86 mm at the coronal end, 0.71 mm at the center, and 0.87 mm at the apical tip. The average angular discrepancy was 1.76 degrees. Conclusions: The use of stereolithographic surgical guides based on CBCT data allows for accurate orthodontic mini screw insertion without damaging neighboring anatomic structures. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:860-865

The suitability of different FEA models for studying root fractures caused by wedge effect

Finite element analysis (FEA) utilizing models with different levels of complexity are found in the literature to study the tendency to vertical root fracture caused by post intrusion (""wedge effect""). The objective of this investigation was to verify if some simplifications used in bi-dimensional FEA models are acceptable regarding the analysis of stresses caused by wedge effect. Three plane strain (PS) and two axisymmtric (Axi) models were studied. One PS model represented the apical third of the root entirely, in dentin (PS-nG). The other models included gutta-percha in the apical third, and differed regarding dentin-post relationship: bonded (PS-B and Axi-B) or nonbonded (PS-nB and Axi-nB). Mesh discretization and material properties were similar for all cases. Maximum principal stress (sigma(max)) was analyzed as a response to a 165 N longitudinal load. Stress magnitude and orientation varied widely (PS-nG: 10.3 MPa; PS-B: 0.8 MPa; PS-nB: 10.4 MPa; Axi-13: 0.2 MPa, Axi-nB: 10.8 MPa). Axi-nB was the only model where all (sigma(max) vectors at the apical third were perpendicular to the model plane. Therefore, it is adequate to demonstrate the tendency to vertical root fractures caused by wedge effect. Axi-13 showed only part of the (sigma(max) perpendicular to the model plane while PS models showed sigma(max) on the model plane. In these models, sigma(max) orientation did not represent a situation where vertical root fracture would occur due to wedge effect. Adhesion between post and dentin significantly reduced (c) 2007 Wiley Periodicals, Inc.

Incidence, morphology and morphometry of the foramen of Vesalius: complementary study for a safer planning and execution of the trigeminal rhizotomy technique

The foramen of Vesalius (FV) is located in the greater wing of the sphenoid bone between the foramen ovale (FO) and the foramen rotundum in an intracranial view. The FO allows the passage of the mandibular branch of trigeminal nerve, which is the target of the trigeminal radiofrequency rhizotomy. We analyzed its location, morphology, morphometry and interrelation among other foramina. 400 macerated adult human skulls were examined. A digital microscope (Dino-Lite plus(A (R))) was used to capture images from the FV. A digital caliper was used to perform the measurements of the distance between the FV and other foramina (FO, foramen spinosum and the carotid canal) in an extracranial view of the skull base. In the 400 analyzed skulls, the FV was identified in 135 skulls (33.75%) and absent on both sides in 265 skulls (66.25%). The FV was observed present bilaterally in 15.5% of the skulls. The incidence of unilateral foramen was 18.25% of the skulls of which 7.75% on right side and 10.5% on left side. The diameter of the FV was measured and we found an average value of 0.65 mm, on right side 0.63 mm and on the left side 0.67 mm. We verified that positive correlations were statistically significant among the three analyzed distances. This study intends to offer specific anatomical data with morphological patterns (macroscopic and mesoscopic) to increase the understanding of the FV features as frequency, incidence and important distances among adjacent foramina.

Impacted Lower Third Molar Fused with a Supernumerary Tooth - Diagnosis and Treatment Planning Using Cone-Beam Computed Tomography

Osny Ferreira-Junior, Luciana Dorigatti de Avila, Marcelo Bonifacio da Silva Sampieri, Eduardo Dias-Ribeiro, Weiliang Chen, Song Fan. Impacted Lower Third Molar Fused with a Supernumerary Tooth-Diagnosis and Treatment Planning Using Cone-Beam Computed Tomography. International Journal of Oral Science, 1(4): 224-228, 2009 This paper reported a case of fusion between an impacted third molar and a supernumerary tooth, in which a surgical intervention was carried out, with the objective of removing the dental elements. The panoramic radiography was complemented by the Donovan`s radiographic technique; but because of the proximity of the dental element to the mandibular ramus, it was not possible to have a final fusion diagnosis. Hence, the Cone-Beam Computed Tomography-which provides precise three-dimensional information-was used to determinate the fusion diagnosis and also to help in the surgical planning. In this case report we observed that the periapical, occlusal and panoramic were not able to show details which could only be examined through the cone-beam computed tomography.

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.