Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multipinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target’s radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals.

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration.

Antioxidant effect of mogrosides against oxidative stress induced by palmitic acid in mouse insulinoma NIT-1 cells

Excessive oxidative stress in pancreatic β cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.

Five models of capitalism

Besides analyzing capitalist societies historically and thinking of them in terms of phases or stages, we may compare different models or varieties of capitalism. In this paper I survey the literature on this subject, and distinguish the classification that has a production or business approach from those that use a mainly political criterion. I identify five forms of capitalism: among the rich countries, the liberal democratic or Anglo-Saxon model, the social or European model, and the endogenous social integration or Japanese model; among developing countries, I distinguish the Asian developmental model from the liberal-dependent model that characterizes most other developing countries, including Brazil.

A System for Models of First Order Theories

If you want to know whether a property is true or not in a specific algebraic structure,you need to test that property on the given structure. This can be done by hand, which can be cumbersome and erroneous. In addition, the time consumed in testing depends on the size of the structure where the property is applied. We present an implementation of a system for finding counterexamples and testing properties of models of first-order theories. This system is supposed to provide a convenient and paperless environment for researchers and students investigating or studying such models and algebraic structures in particular. To implement a first-order theory in the system, a suitable first-order language.( and some axioms are required. The components of a language are given by a collection of variables, a set of predicate symbols, and a set of operation symbols. Variables and operation symbols are used to build terms. Terms, predicate symbols, and the usual logical connectives are used to build formulas. A first-order theory now consists of a language together with a set of closed formulas, i.e. formulas without free occurrences of variables. The set of formulas is also called the axioms of the theory. The system uses several different formats to allow the user to specify languages, to define axioms and theories and to create models. Besides the obvious operations and tests on these structures, we have introduced the notion of a functor between classes of models in order to generate more co~plex models from given ones automatically. As an example, we will use the system to create several lattices structures starting from a model of the theory of pre-orders.

Alternative Models of Court Administration

Canadian Judicial Council

Two models of constitutionalism and the legitimacy of law : Dicey or Marshall ?

The article was first published in the Oxford University Commonwealth Law Journal.

The invisibility of privilege: a critique of intersectional models of identity

In this paper, I argue that intersectionality, the prevailing way of conceptualizing the relation between axes or systems of oppression (race, class, gender), illicitly imports the very model it purports to overcome: that is, the unitary model of identity. I first define “intersectionality” and distinguish between three senses that are frequently conflated. Then I subject the model to an analytic critique, revealing its hidden presuppositions about identity. Finally, I suggest that solidarity serves as a better norm for feminist practice than inclusion of “difference,” which seems to be the norm underlying many intersectional accounts.

The process of anxiety reduction during the treatment of social phobia with an interpersonal approach : alone or combined with paroxetine

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Induction of astrocytic cyclooxygenase-2 in epileptic patients with hippocampal sclerosis.

Induction of cyclooxygenase-2 (COX-2) has been described in a wide range of neurological diseases including animal models of epilepsy. The present study was undertaken to assess COX-2 expression in hippocampal biopsies from patients with therapy-refractive temporal lobe epilepsy (TLE). For this purpose, hippocampal CA1 subfield was dissected from epileptic patients with (n=5) or without (n=2) hippocampal sclerosis (HS). COX-2 expression was investigated using immunohistochemistry and semi-quantitative RT-PCR. COX-2 immunoreactivity in TLE patient material in the absence of HS was restricted to a few neurons of the hippocampus. In the presence of HS, on the other hand, a significant induction of astrocytic COX-2 immunoreactivity associated with a concomitant increase in the steady-state level of COX-2 mRNA was observed in the CA1 subfield. These findings suggest that induction of astrocytic COX-2 is implicated in the pathogenesis of HS in TLE and is consistent with the previous findings of increased concentrations of prostaglandins in the cerebrospinal fluid of these patients.

Comparison of epicardial mapping and noncontact endocardial mapping in dog experiments and computer simulations

La fibrillation auriculaire, l'arythmie la plus fréquente en clinique, affecte 2.3 millions de patients en Amérique du Nord. Pour en étudier les mécanismes et les thérapies potentielles, des modèles animaux de fibrillation auriculaire ont été développés. La cartographie électrique épicardique à haute densité est une technique expérimentale bien établie pour suivre in vivo l'activité des oreillettes en réponse à une stimulation électrique, à du remodelage, à des arythmies ou à une modulation du système nerveux autonome. Dans les régions qui ne sont pas accessibles par cartographie épicardique, la cartographie endocardique sans contact réalisée à l'aide d'un cathéter en forme de ballon pourrait apporter une description plus complète de l'activité auriculaire. Dans cette étude, une expérience chez le chien a été conçue et analysée. Une reconstruction électro-anatomique, une cartographie épicardique (103 électrodes), une cartographie endocardique sans contact (2048 électrodes virtuelles calculées à partir un cathéter en forme de ballon avec 64 canaux) et des enregistrements endocardiques avec contact direct ont été réalisés simultanément. Les systèmes d'enregistrement ont été également simulés dans un modèle mathématique d'une oreillette droite de chien. Dans les simulations et les expériences (après la suppression du nœud atrio-ventriculaire), des cartes d'activation ont été calculées pendant le rythme sinusal. La repolarisation a été évaluée en mesurant l'aire sous l'onde T auriculaire (ATa) qui est un marqueur de gradient de repolarisation. Les résultats montrent un coefficient de corrélation épicardique-endocardique de 0.8 (expérience) and 0.96 (simulation) entre les cartes d'activation, et un coefficient de corrélation de 0.57 (expérience) and 0.92 (simulation) entre les valeurs de ATa. La cartographie endocardique sans contact apparait comme un instrument expérimental utile pour extraire de l'information en dehors des régions couvertes par les plaques d'enregistrement épicardique.

How fast and how often: the pharmacokinetics of drug use are decisive in addiction

How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, ‘spiking’ brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

Computational Models of Object Recognition in Cortex: A Review

Understanding how biological visual systems perform object recognition is one of the ultimate goals in computational neuroscience. Among the biological models of recognition the main distinctions are between feedforward and feedback and between object-centered and view-centered. From a computational viewpoint the different recognition tasks - for instance categorization and identification - are very similar, representing different trade-offs between specificity and invariance. Thus the different tasks do not strictly require different classes of models. The focus of the review is on feedforward, view-based models that are supported by psychophysical and physiological data.