Sexually dimorphic postural adjustments during vertical behaviour are altered in a unilateral 6-OHDA rat model of Parkinson's disease

The study of sex differences in the onset, progression and symptoms of Parkinson's disease, in humans, has led to mixed results. In this study, we used a unilateral 6-hydroxydopamine (6-OHDA) lesion animal model of Parkinson's disease, to address whether there are sex differences in the composition of the movements used during vertical exploration within a confined cylinder. Tyrosine hydroxylase staining and apomorphine induced rotation were used to confirm lesion magnitude. There were no sex differences or lesion effects in the frequency of occurrence of a vertical bout or the average time spent vertical. Both male and female 6-OHDA animals exhibited equal impairments in the use of the forelimbs during vertical exploration. 6-OHDA males, as compared to 6-OHDA females, however, had a significant reduction in the use of their hindlimbs. An analysis of hindlimb step direction revealed that while sham females were more likely to step forward, sham males were more likely to step backwards during a vertical bout. This sex difference was no longer present in the 6-OHDA animals. Finally, 6-OHDA males were significantly more likely to place their dorsal surface in contact with the wall of the cylinder to maintain an upright posture during a vertical bout than animals in any other condition. These results demonstrate that the use of a confined cylinder task is appropriate for the kinematic analysis of sex differences in vertical behaviour and show that there are sex differences in motor behaviour in an animal model of human Parkinson's disease.     

Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro

Isothiocyanates (ITCs) and indoles derived from cruciferous vegetables possess growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. ITCs like sulforaphane (SFN) are cytotoxic, whereas indoles including indole-3-carbinol or its condensation product 3,3'-diindolylmethane (DIM) are acting by cytostatic mechanisms in human colon cancer cell lines. In the present study, we have investigated the impact of defined combinations of SFN and DIM (ratio 1:4, 1:2, 1:1, 2:1 and 4:1) on cell proliferation, cell-cycle progression and apoptosis induction in cultured 40-16 colon carcinoma cells. Calculations of combination effects were based on the method of Chou et al. (1984) Adv. Enzyme Regul., 22, 27-55, and were expressed as a combination index (CI) with CI < 1, CI = 1 or CI > 1 representing synergism, additivity or antagonism, respectively. Interestingly, at a total drug concentration of 2.5 microM, all combinations of SFN and DIM were antagonistic. With increasing concentrations, the antagonistic effect gradually turned into a synergistic interaction at the highest combined cytotoxic concentration of 40 microM. Cell-cycle analyses with SFN:DIM ratios of 1:1, 1:2 and 1:4 and total concentrations between 10 and 25 microM confirmed antagonism at low and additive effects at higher doses. SFN (10 microM) in combination with DIM (10 microM) resulted in strong G(2)/M cell-cycle arrest, which was not observed with either compound alone. Our results indicate that cytotoxic concentrations of SFN:DIM combinations affect cell proliferation synergistically. At low total concentrations (below 20 microM), which are physiologically more relevant, the combined broccoli compounds showed antagonistic interactions in terms of cell growth inhibition. These data stress the need for elucidating mechanistic interactions for better predicting beneficial health effects of bioactive food components.     

Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.     

Differential effects on forelimb grasping behavior induced by fetal dopaminergic grafts in hemiparkinsonian rats

Skilled forelimb movements depend on an intact dopaminergic (DA) neurotransmission and are substantially impaired in the unilateral rat model of Parkinson's disease. It has remained unclear, however, to what extent reaching and grasping movements can be influenced by intrastriatal transplantation of fetal DA neurons. Here an extensive behavioral assessment of skilled forelimb movement patterns in hemiparkinsonian and DA-grafted rats was carried out. Good DA graft survival was accompanied by a compensation of drug-induced rotational asymmetries. Interestingly, skilled forelimb use was significantly improved in transplanted animals as compared to lesion-only animals in the staircase test. Qualitative analysis of single forelimb reaching movement components revealed dissociable patterns of graft effects: while some movement components in grafted animals improved, others remained unchanged or even deteriorated. These findings provide novel insights into the complex interactions of graft-derived restoration of DA neurotransmission and skilled forelimb behavior.     

TNM staging with FDG-PET/CT in patients with primary head and neck cancer

Purpose PET/CT, PET+CT, and CT were compared concerning accuracies in TNM staging and malignancy detection in head and neck cancer. The impact of PET/CT compared to the other imaging modalities on therapy management was assessed. Materials and methods Fifty-five patients with suspected head and neck primary cancer underwent whole-body FDG-PET/CT. PET/CT and PET+CT were evaluated by a nuclear medicine physician and a radiologist; CT was evaluated by two radiologists, PET by two nuclear physicians. Histopathology served as the standard of reference. Differences between the staging modalities were tested for statistical significance by McNemar’s test. Results Overall TNM-staging and T-staging with PET/CT were more accurate than PET+CT and CT alone (p < 0.05). PET/CT was marginally more accurate than CT alone in N-staging (p = 0.04); no statistically significant difference was found when compared to PET+CT for N-staging. PET/CT altered further treatment in 13 patients compared to CT only and in 7 patients compared to PET+CT. Conclusion Combined PET/CT proved to be partly more accurate in assessing the overall TNM-stage than CT and PET+CT. These results were based on a higher accuracy concerning the T-stage, mainly in patients with metallic implants and marginally the N-stage. Therapy decisions have been influenced in a substantial number of patients. PET/CT might be considered as a first line diagnostic tool in patients with suspected primary head and neck cancer.     

Do visual perspective tasks need theory of mind?

Reviews [Frith, U., Frith, C.D., 2003. Development and neurophysiology of mentalising. Philos. Trans. R. Soc., B 358, 685-694.] of several imaging studies report robust involvement of medial prefrontal cortex (MPFC) in "theory of mind" (ToM) tasks. Surprisingly, this activation is notably absent when judging another person's visual perspective [Vogeley, K., May, M., Ritzl, A., Falkai, P., Zilles, K., Fink, G.R., 2004. Neural correlates of first-person perspective as one constituent of human self-consciousness. J. Cogn. Neurosci. 16, 817-827.]. The objective of our study was to see whether this activation can be recovered when the difference between what observers see is clearly one of perspectives (in front vs. behind) and not potentially a difference in what observers are looking at. Despite this change, there was still no apparent activation of MPFC. We did find activation in the temporo-parietal junction (TPJ) recently emphasized as centrally involved in processing false belief stories [Saxe, R., Kanwisher, N., 2003. People thinking about thinking people: The role of the temporo-parietal junction in "theory of mind". NeuroImage 19, 1835-1842.], which also create a stark contrast of perspectives. By integrating extant neurophysiological evidence on theory of mind processing, we suggest that the dorsal part of the TPJ region is responsible for representing perspective differences and making behavioral predictions, while the more ventral part of TPJ and the MPFC region is responsible for predicting behavioral consequences and the MPFC also emotional consequences of mental states.     

The Influence of Superabsorbent Polymers and Nanosilica on the Hydration Process and Microstructure of Cementitious Mixtures

Superabsorbent polymers (SAPs) are known to mitigate the development of autogenous shrinkage in cementitious mixtures with a low water-to-cement ratio. Moreover, the addition of SAPs promotes the self-healing ability of cracks. A drawback of using SAPs lies in the formation of macropores when the polymers release their absorbed water, leading to a reduction of the mechanical properties. Therefore, a supplementary material was introduced together with SAPs, being nanosilica, in order to obtain an identical compressive strength with respect to the reference material without additives. The exact cause of the similar compressive behaviour lies in the modification of the hydration process and subsequent microstructural development by both SAPs and nanosilica. Within the present study, the effect of SAPs and nanosilica on the hydration progress and the hardened properties is assessed. By means of isothermal calorimetry, the hydration kinetics were monitored. Subsequently, the quantity of hydration products formed was determined by thermogravimetric analysis and scanning electron microscopy, revealing an increased amount of hydrates for both SAP and nanosilica blends. An assessment of the pore size distribution was made using mercury intrusion porosimetry and demonstrated the increased porosity for SAP mixtures. A correlation between microstructure and the compressive strength displayed its influence on the mechanical behaviour.