Increased training prevents the impairing effect of intra-amygdala infusion of the non-NMDA receptor antagonist CNQX on inhibitory avoidance expression

Intra-amygdala infusion of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prior to testing impairs inhibitory avoidance retention test performance. Increased training attenuates the impairing effects of amygdala lesions and intra-amygdala infusions of CNQX. The objective of the present study was to determine the effects of additional training on the impairing effects of intra-amygdala CNQX on expression of the inhibitory avoidance task. Adult female Wistar rats bilaterally implanted with cannulae into the border between the central and the basolateral nuclei of the amygdala were submitted to a single session or to three training sessions (0.2 mA, 24-h interval between sessions) in a step-down inhibitory avoidance task. A retention test session was held 48 h after the last training. Ten minutes prior to the retention test session, the animals received a 0.5-µl infusion of CNQX (0.5 µg) or its vehicle (25% dimethylsulfoxide in saline). The CNQX infusion impaired, but did not block, retention test performance in animals submitted to a single training session. Additional training prevented the impairing effect of CNQX. The results suggest that amygdaloid non-NMDA receptors may not be critical for memory expression in animals given increased training.

Actus ejusdem, qvatenus ab intra saltem, tam de rebus materiae immersis qvam ejus expertibus formantur, breviter repraesentans

Invokaatio: Q.F.E.J.D.

De ritu excommunicationis intra et extra ecclesiam

Variantti B.

De ritu excommunicationis intra et extra ecclesiam

Variantti A.

De lapidibus viventibus, I. Pet. II:5

Invokaatio: I.N.J.

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonance

Striatal and extrastriatal dopamine D2/3 receptors studied with [11C]raclopride and high-resolution PET

The human striatum is a heterogeneous structure representing a major part of the dopamine (DA) system’s basal ganglia input and output. Positron emission tomography (PET) is a powerful tool for imaging DA neurotransmission. However, PET measurements suffer from bias caused by the low spatial resolution, especially when imaging small, D2/3 -rich structures such as the ventral striatum (VST). The brain dedicated high-resolution PET scanner, ECAT HRRT (Siemens Medical Solutions, Knoxville, TN, USA) has superior resolution capabilities than its predecessors. In the quantification of striatal D2/3 binding, the in vivo highly selective D2/3 antagonist [11C] raclopride is recognized as a well-validated tracer. The aim of this thesis was to use a traditional test-retest setting to evaluate the feasibility of utilizing the HRRT scanner for exploring not only small brain regions such as the VST but also low density D2/3 areas such as cortex. It was demonstrated that the measurement of striatal D2/3 binding was very reliable, even when studying small brain structures or prolonging the scanning interval. Furthermore, the cortical test-retest parameters displayed good to moderate reproducibility. For the first time in vivo, it was revealed that there are significant divergent rostrocaudal gradients of [11C]raclopride binding in striatal subregions. These results indicate that high-resolution [11C]raclopride PET is very reliable and its improved sensitivity means that it should be possible to detect the often very subtle changes occurring in DA transmission. Another major advantage is the possibility to measure simultaneously striatal and cortical areas. The divergent gradients of D2/3 binding may have functional significance and the average distribution binding could serve as the basis for a future database. Key words: dopamine, PET, HRRT, [11C]raclopride, striatum, VST, gradients, test-retest.

Evaluation of the quality of pet foods using fast techniques and official methods

This paper was designed to evaluate the rancidity of 18 pet food samples using the Diamed FATS kits and official AOCS methods for the quantification of free fatty acids, peroxide value and concentrations of malonaldehyde and alkenal in the lipid extracted. Although expiration dates have passed, the samples presented good quality evidencing little oxidative rancidity. The results of this study suggest that the Brazilian pet food market is replete with products of excellent quality due to the competitiveness of this market sector.

Influencia de la deshidratación osmótica y de la adición de cloruro de calcio en la conservación de kivis minimamente procesados

Este trabajo tubo como objetivo estudiar el efecto combinado de la deshidratación osmótica y la influencia del cloruro de calcio en rodajas de kivi sometidos al proceso mínimo. Muestras con y sin deshidratación osmótica fueron almacenadas a 5 °C en embalajes PET. La adición de cloruro de calcio fue realizada durante la deshidratación osmótica. Se evaluaron la pérdida de peso, acidez, sólidos solubles, pH, humedad, coliformes, hongos y levaduras en las muestras hasta 15 días de almacenamiento. La deshidratación osmótica consistió en la inmersión de las rodajas de kivi en solución de sacarosa a 60% y en solución de sacarosa (60%) con adición de cloruro de calcio (0,1 M), ambos tratamientos se realizaron a temperatura ambiente (25 °C) por 24 horas y relación fruta:solución de 1:5. Los resultados mostraron que el pré-tratamiento osmótico con adición de cloruro de calcio aumentó la vida útil hasta 15 días, en cuanto las rodajas tratadas por osmodeshidratación sin adición de sal presentaron vida útil de 12 días. Sensorialmente, los consumidores prefirieron las rodajas de kivi procesadas con pré-tratamiento osmótico y adición de cloruro de calcio.

The alpha2C-adrenoceptor as a neuropsychiatric drug tar-get - PET studies in human subjects

Positron emission tomography imaging has both academic and applied uses in revealing the distribution and density of different molecular targets in the central nervous system. Following the significant progress made with the dopamine D2 receptor, advances have been made in developing PET tracers to allow analysis of receptor occupancy of many other receptor types as well as evaluating changes in endogenous synaptic transmitter concentrations of transmitters e.g. serotonin and noradrenaline. Noradrenergic receptors are divided into α1-, α2- and β-adrenoceptor subfamilies, in humans each of which is composed of three receptor subtypes. The α2-adrenoceptors have an important presynaptic auto-inhibitory function on noradrenaline release but they also have postsynaptic roles in modulating the release of other neurotransmitters, such as serotonin and dopamine. One of the subtypes, the α2C-adrenoceptor, has been detected at distinct locations in the central nervous system, most notably the dorsal striatum. Several serious neurological conditions causing dementia, Alzheimer’s disease and Parkinson’s disease have been linked to disturbed noradrenergic signaling. Furthermore, altered noradrenergic signaling has also been implicated in conditions like ADHD, depression, anxiety and schizophrenia. In order to benefit future research into these central nervous system disorders as well as being useful in the clinical development of drugs affecting brain noradrenergic neurotransmission, validation work of a novel tracer for positron emission tomography studies in humans was performed. Altogether 85 PET imaging experiments were performed during four separate clinical trials. The repeatability of [11C]ORM-13070 binding was tested in healthy individuals, followed by a study to evaluate the dose-dependent displacement of [11C]ORM-13070 from α2C-adrenoceptors by a competing ligand, and the final two studies examined the sensitivity of [11C]ORM-13070 binding to reflect changes in endogenous noradrenaline levels. The repeatability of [11C]ORM-13070 binding was very high. The binding properties of the tracer allowed for a reliable estimation of α2C-AR occupancy by using the reference tissue ratio method with low test-retest variability. [11C]ORM-13070 was dose-dependently displaced from its specific binding sites by the subtype-nonselective α2-adrenoceptor antagonist atipamezole, and thus it proved suitable for use in clinical drug development of novel α2C-adrenoceptor ligands e.g. to determine the best doses and dosing intervals for clinical trials. Convincing experimental evidence was gained to support the suitability of [11C]ORM-13070 for detecting an increase in endogenous synaptic noradrenaline in the human brain. Tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, although statistical significance was not reached. Thus, the investigation was unable to fully validate [11C]ORM-13070 for the detection of pharmacologically evoked reductions in noradrenaline levels.

EXPLOITING SCENARIO PLANNING FOR STRATEGIC ASSESSMENT OF THE EXTERNAL BUSINESS ENVIRONMENT Future insights of the European pet food sector

The purpose of this study is to explore how scenarios can be exploited in strategic assessment of the external business environment. One of the key challenges for managers worldwide is to adapt their businesses to the ever-changing business environment. As the companies’ external business environment is constantly presenting new opportunities and threats, it is extremely important that companies continuously monitor the possible changes happening around it. As the speed of change rises, assessing the future has become more and more vital. The study was conducted as an exploratory research and the research strategy was influenced by scenario planning and case study strategy. The study examined the European pet food sector from the future point of view. Qualitative study was chosen as research approach and empirical data was collected primarily by seven expert interviews. The secondary data about the sector was applied as complementary empirical data. In the theoretical part of the research it was discovered that nowadays, traditional analysis frameworks are ill-suited for strategic assessment of the external business environment. This is why a self-created combination framework for analysis was employed both as study’s theoretical framework and analysis technique. Furthermore, the framework formed the base for interview questions. Both in theoretical and the empirical part of the study it was found that today, in strategic assessment of the external business environment, besides setting focus on the current situation, it is important to concentrate also on the future. The traditional analysis frameworks offer a good starting point for collecting relevant data but they do not encourage conducting a deeper analysis. By adding characteristics from scenario planning to these more traditional tools, a new analysis framework was created, which ensured the more comprehensive analysis. By understanding the interconnections between discovered phenomena and changes, and by recognizing uncertainties, the user is helped to reflect the environment more profoundly. The contributions of the study are both theoretical and managerial. A new analysis framework strives to answer to the current needs for strategic assessment of external business environment and the framework was tested in the context of European pet food sector. When it comes to managerial contributions, the importance lies in understanding the future. Managers must take future into account and understand that future includes various possibilities which all must be reflected