Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies

7-ketocholesterol (7-KC) differs from cholesterol by a functional ketone group at C7. It is an oxygenated cholesterol derivative (oxysterol), commonly present in oxidized low-density lipoprotein (LDL). Oxysterols are generated and participate in several physiologic and pathophysiologic processes. For instance, the cytotoxic effects of oxidized LDL have been widely attributed to bioactive compounds like oxysterols. The toxicity is in part due to 7-KC. Here we aimed to demonstrate the possibility of incorporating 7-KC into the synthetic nanoemulsion LDE, which resembles LDL in composition and behavior. This would provide a suitable artificial particle resembling LDL to study 7-KC metabolism. We were able to incorporate 7-KC in several amounts into LDE. The incorporation was evaluated and confirmed by several methods, including gel filtration chromatography, using radiolabeled lipids. The incorporation did not change the main lipid composition characteristics of the new nanoparticle. Particle sizes were also evaluated and did not differ from LDE. In vivo studies were performed by injecting the nanoemulsion into mice. The plasma kinetics and the targeted organs were the same as described for LDE. Therefore, 7-KC-LDE maintains composition, size and some functional characteristics of LDE and could be used in experiments dealing with 7-ketocholesterol metabolism in lipoproteins.

Model for Differential Nursing Diagnosis of Alterations in Urinary Elimination Based on Fuzzy Logic

Nursing diagnoses associated with alterations of urinary elimination require different interventions, Nurses, who are not specialists, require support to diagnose and manage patients with disturbances of urine elimination. The aim of this study was to present a model based on fuzzy logic for differential diagnosis of alterations in urinary elimination, considering nursing diagnosis approved by the North American Nursing Diagnosis Association, 2001-2002. Fuzzy relations and the maximum-minimum composition approach were used to develop the system. The model performance was evaluated with 195 cases from the database of a previous study, resulting in 79.0% of total concordance and 19.5% of partial concordance, when compared with the panel of experts. Total discordance was observed in only three cases (1.5%). The agreement between model and experts was excellent (kappa = 0.98, P < .0001) or substantial (kappa = 0.69, P < .0001) when considering the overestimative accordance (accordance was considered when at least one diagnosis was equal) and the underestimative discordance (discordance was considered when at least one diagnosis was different), respectively. The model herein presented showed good performance and a simple theoretical structure, therefore demanding few computational resources.

Model-Predicted Performance of Second-Trimester Down Syndrome Screening With Sonographic Prenasal Thickness

Objective. The purpose of this study was to estimate the Down syndrome detection and false-positive rates for second-trimester sonographic prenasal thickness (PT) measurement alone and in combination with other markers. Methods. Multivariate log Gaussian modeling was performed using numerical integration. Parameters for the PT distribution, in multiples of the normal gestation-specific median (MoM), were derived from 105 Down syndrome and 1385 unaffected pregnancies scanned at 14 to 27 weeks. The data included a new series of 25 cases and 535 controls combined with 4 previously published series. The means were estimated by the median and the SDs by the 10th to 90th range divided by 2.563. Parameters for other markers were obtained from the literature. Results. A log Gaussian model fitted the distribution of PT values well in Down syndrome and unaffected pregnancies. The distribution parameters were as follows: Down syndrome, mean, 1.334 MoM; log(10) SD, 0.0772; unaffected pregnancies, 0.995 and 0.0752, respectively. The model-predicted detection rates for 1%, 3%, and 5% false-positive rates for PT alone were 35%, 51%, and 60%, respectively. The addition of PT to a 4 serum marker protocol increased detection by 14% to 18% compared with serum alone. The simultaneous sonographic measurement of PT and nasal bone length increased detection by 19% to 26%, and with a third sonographic marker, nuchal skin fold, performance was comparable with first-trimester protocols. Conclusions. Second-trimester screening with sonographic PT and serum markers is predicted to have a high detection rate, and further sonographic markers could perform comparably with first-trimester screening protocols.

Histologic Study of Acute Vocal Fold Wound Healing After Corticosteroid Injection in a Rabbit Model

Objectives: Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects of wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. Methods: A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for qunatification of collagen depostion. Results: There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collage deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). Conclusions: The present results suggest that dexamethasone reduces collagen depostion during acute vocal fold wound healing.

A Graphical Representation Model for Telemedicine and Telehealth Center Sustainability

This study shows the creation of a graphical representation after the application of a questionnaire to evaluate the indicative factors of a sustainable telemedicine and telehealth center in Sao Paulo, Brazil. We categorized the factors into seven domain areas: institutional, functional, economic-financial, renewal, academic-scientific, partnerships, and social welfare, which were plotted into a graphical representation. The developed graph was shown to be useful when used in the same institution over a long period and complemented with secondary information from publications, archives, and administrative documents to support the numerical indicators. Its use may contribute toward monitoring the factors that define telemedicine and telehealth center sustainability. When systematically applied, it may also be useful for identifying the specific characteristics of the telemedicine and telehealth center, to support its organizational development.

Response to AIDS in Brazil: contributions of social movements and the sanitary reform

This paper briefly outlines how the political scenario and the mobilization of different actors have contributed to the construction of a public health policy in response to the AIDS epidemics in Brazil. Three factors are presented and discussed: the political context of the 1980s, characterized by redemocratization, growth of social movements, and consolidation of the Brazilian health care reform; the socio-cultural context of the 1970s and 1980s, characterized by achievement of individual freedom, which was key to the organization of the AIDS movement; and finally the actions carried out in the international scenario to support the sustainability of the Brazilian domestic policy and the reinforcement of a global response to face the epidemics in lower-middle income economies.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death

Background: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. Material/Methods: Ten dogs (21.3 +/- 0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without ally additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. Results: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0 +/- 0.2 VS. 2.8 +/- 2.8 L/min) and PVBF (687 +/- 114 vs. 623 +/- 130 ml/min) was observed, whereas HABF (277 33 vs. 134 28 ml/min, p<0.005) remained lower than baseline values. Conclusions: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Social dysfunction in bipolar disorder: pilot study

Objective: The purpose of the present study was to assess the social skills of euthymic patients with bipolar disorder. Methods: A group of 25 outpatients with bipolar disorder type I were evaluated in comparison with a group of 31 healthy volunteers who were matched in terms of level of education, age, sex and intelligence. Both groups were assessed using a self-report questionnaire, the Brazilian Inventario de Habilidades Sociais (IHS, Social Skills Inventory). Two Wechsler Adult Intelligence Scale subtests ( Picture Arrangement and Comprehension) were also used in order to assess subject ability to analyse social situations and to make judgements, respectively. Results: Patients with bipolar disorder had lower IHS scores for the domains that assessed conversational skills/social self-confidence and social openness to new people/situations. Patients with anxiety disorders had high scores for the domain that assessed self-confidence in the expression of positive emotions. No differences were found between patients and controls in performance on the Wechsler Adult Intelligence Scale Picture Arrangement and Comprehension subtests. Conclusions: Euthymic patients with bipolar disorder present inhibited and overattentive behaviour in relation to other people and their environment. This behaviour might have a negative impact on their level of social functioning and quality of life.

PHOTOELASTIC ANALISYS OF A HUMAN VERTEBRA MODEL WITH PEDICULAR SCREW

Introduction: The vertebrae fixation system using pedicular screws is one of the most efficient methods to treat vertebral spine pathologies. When the screw is submitted to pullout strength, it causes internal tension near the medullar canal and this situation can be analyzed by using the photoelasticity technique. Objective: Were analyzed those internal tensions near the medullar canal of photoelastic vertebra models using different sizes of screws of the vertebral fixation system submitted to pullout strength. Methods: A lumbar vertebral model made of photoelastic material with three different USS1-type pedicular screw sizes (5, 6, and 7 mm) was used. The internal tensions around the screw were tested in 12 predetermined points by a plain transmission polaroscope. Results: The areas of greater tension concentration were between the medullar canal and the curves of the transverse process. Comparing the maximum average pulling tension, statistical differences were observed between screws 5 and 7, and 6 and 7. On the other hand, for screws 5 and 6, there were no significant differences. Conclusion: The study evidenced that the internal tensions are greater in irregular areas, next to the medullar canal, showing that this is a critical region.

Newly Formed Bone in Mandible Decortication Experimental Model Using rhBMP-2 Evaluated by Densitometric Study

The purpose of this study was to evaluate the newly formed bone, comparing two different carriers for rhBMP-2, using the decortication and nondecorticatication surgical technique in Wistar rat mandibles, evaluated by radiographic densitometry method. It was used fifty six animals according to specific treatment, which were sacrificed after 3 and 6 weeks after this. It was concluded that the decortication surgical technique was able to optimize the osteoinduction properties of the rhBMP-2, independently of the material carrier used and the period of time, according to radiographic densitometry technique.

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation

Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gamma delta(+) and CD4(+)CD25(+)Foxp3(+) cells in Peyer`s patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. Conclusion A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.

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).

Social anxiety disorder: studies of instrument validation for the Brazilian context

Social anxiety disorder (SAD) is a highly prevalent condition even though its recognition and diagnosis are underestimated by both patients and clinicians. In view of the importance of assessment scales for systematic diagnosis in psychiatry, the objective of this investigation was to present studies of validation for the Brazilian population of three instruments for the assessment of different aspects of SAD. The following psychometric studies were carried out: a) discriminative validity of the Mini Social Phobia Inventory (Mini-SPIN-MS), a reduced instrument for the screening of SAD; b) reliability and discriminative validity of the Brief Social Phobia Scale (BSPS), a hetero-applied instrument for the assessment of different aspects of SAD, and c) discriminative validity of the items and subscales of the Self-Statements during Public Speaking Scale (SSPS), an instrument for the assessment of cognitive aspects related to public speaking. All instruments showed excellent psychometric qualities, especially indicators of discrimination between persons with and without SAD, with diagnostic confirmation by the Structured Clinical Interview for DSM-IV (SCID-IV). It was concluded that this set of instruments, with specificity regarding their objectives, could be of great clinical usefulness, especially for the Brazilian population that, until recently, had no such resources for the measurement and assessment of the different aspects of SAD. New multicenter and intercultural studies may provide further information about cultural influences on SAD.

Effects of beta-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: Further evidence of antidepressant properties

The chronic mild stress (CMS) model has been used as an animal model of depression which induces anhedonic behavior in rodents. The present study was aimed to evaluate the behavioral and physiological effects of administration of P-carboline harmine in rats exposed to CMS Procedure. To this aim, after 40 days of exposure to CMS procedure, rats were treated with harmine (15 mg/kg/day) for 7 days. In this study, sweet food consumption, adrenal gland weight, adrenocorticotrophin hormone (ACTH) levels, and hippocampal brain-derived-neurotrophic factor (BDNF) protein levels were assessed. Our findings demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, increase ACTH circulating levels in rats and increase BDNF protein levels. Interestingly, treatment with harmine reversed anhedonia, the increase of adrenal gland weight, normalized ACTH circulating levels and BDNF protein levels. Finally, these findings further support the hypothesis that harmine could be a new pharmacological tool for the treatment of depression. (C) 2009 Elsevier Inc. All rights reserved.