Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli

Long-term survival after initial hospital admission for peripheral arterial disease in the lower extremities

ABSTRACT: Background As the population ages, peripheral arterial disease (PAD) in the lower extremities will become a larger public health problem. Awareness in patients as well clinicians of the high risk of morbidity and mortality is important but seems currently low. Insights in absolute mortality risks following admission for PAD in the lower extremities can be useful to improve awareness as they are easy to interpret. Methods A nationwide cohort of 4,158 patients with an initial admission for PAD in the lower extremities was identified through linkage of the national hospital and population register in 1997 and 2000. Results Over 60% of 4,158 patients were men. 28 days, 1 year and 5 year mortality risk were 2.4%, 10.3% and 31.0% for men and 3.5%, 10.4% and 27.4% for women. Coronary heart disease and stroke were frequent cause of death. Five years mortality risk was higher for men compared to women (HR 1.36, 95% CI 1.21-1.53). Conclusions Our findings demonstrate that, 5 year mortality risk is high, especially in men and comparable to that of patients admitted for acute myocardial infarction or ischemic stroke. Though, in general population the awareness of the severity of PAD in the lower extremities is significantly lower than that for any other cardiovascular disease and it seems that cardiovascular risk factor management for prevention in PAD patients is very modes

Enhanced pharmacological efficacy of sumatriptan due to modification of its physicochemical properties by inclusion in selected cyclodextrins

The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examined in vitro in a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition, 1H and 13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied

PI3Kinase signaling in glioblastoma

Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

Comparison of contrast-enhanced multidetector computed tomography angiography and splenoportography for the evaluation of portosystemic-shunt occlusion after cellophane banding in dogs

BACKGROUND Many patients with a congenital extrahepatic portosystemic shunt (PSS) do not tolerate an immediate shunt closure. Therefore, slow progressive techniques were developed. To evaluate the success of shunt closure diagnostic imaging is essential to identify possible residual blood flow through the shunt vessel. There is a lack of information about the reliability of computed tomography angiography (CTA) for evaluating residual flow through a PSS after treatment. The purpose of this prospective study was to compare the results of CTA with splenoportography. Three months after cellophane banding CTA and splenoportography were performed in 20 dogs and reviewed by three independent examiners, respectively. In both imaging modalities the presences of a residual shunt was judged as present or absent and the extent of visibility of portal vasculature was recorded. RESULTS Based on the evaluation of the splenoportography residual flow through shunt was present in 6 dogs. The classification of residual shunt present or absent showed a substantial to perfect agreement (κ = 0.65-1.00) between the observers in splenoportography and a slight to moderate agreement (κ = 0.11-0.51) for CTA. Sensitivity and specificity varied between 0.50 and 1.00 and 0.57-0.85, respectively. Significant correlation between CTA and splenoportography for the classification of residual shunt was present only in one observer but not in the other two. CONCLUSION More studies were classified as residual shunt positive with CTA compared to splenoportography. It remains unclear which methods do reflect reality better and thus which method is superior. The greater inter-rater agreement for splenoportography suggests a greater reliability of this technique