Mechanical flutter stimulation induces a lasting response in the sensorimotor cortex as revealed with BOLD fMRI

It has been recently shown that 20 min of mechanical flutter stimulation induces lasting motor cortical excitability changes, as assessed by transcranial magnetic stimulation in relaxed hand muscles. The present functional magnetic resonance imaging (fMRI) study aims to examine if such neuromodulatory changes are reflected in the BOLD signal during a motor test. Therefore, two groups were recruited: one group receiving whole‐hand flutter stimulation with a frequency of 25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM group, n = 22). As motor test finger‐to‐thumb tapping was performed to activate a wide sensorimotor network during the fMRI measurements. Three fMRI measurements were obtained with this test: before stimulation (PRE), after stimulation (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were defined: primary motor area (M1), primary somatosensory area (S1), and supplementary motor area. In the absence of baseline differences between both groups, the FSTIM group showed increased movement‐related brain activations compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed increased blood‐oxygenation‐level‐dependent (BOLD) responses within contralateral S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory effects within S1 and M1 obviously reflect neuroplastic changes associated with augmented cortical excitability. These findings are of high clinical relevance, for example, to improve the treatment of stroke patients. Hum Brain Mapp 34:2767–2774, 2013. © 2012 Wiley Periodicals, Inc.     

Red cell antioxidant enzymes and prognostic indexes in patients with burns

Red cell superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were measured in 66 burned patients (57 men, 9 women, age 16–78 years). BSAB varied from 15 to 93% and ABSI from 3 to 14 points. In the first week after injury the activity of SOD was significantly decreased as compared with the activity of the enzymes in the control group and was also below the reference values. Later the activity of SOD increased up to the normal range. The activity of CAT followed a similar pattern but the differences were not significant. No significant changes in red cell GPX were found during the monitored period. We did not find any significant association between the antioxidant enzyme activities and the markers of burns severity. On the other side there was a significant indirect association between the change of SOD activity (calculated as a difference between the first week values after the injury and the activities measured later) and BSAB.     

Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study

Central cholinergic dysfunction has been reported in patients with Parkinson?s disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neuropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.     

Immunhistochemische Untersuchung des Kollagen-Typ-I-Gehalts der Gingiva bei Dysostosis cleidocranialis

Background

Patients with cleidocranial dysplasia (CCD) present a thickend and fibrotic gingiva.

Purpose

To the best of our knowledge it was analysed for the first time, whether this is correlated with an increased rate of collagen I in oral mucosa.

Patients and methods

27 soft tissue biopsies of six CCD-patients and 17 tissue samples of 12 healthy persons were labled with a monoclonal antibody against collagen I and the bound antibodies were detected with alkaline phosphatase-anti-alkaline phophatase-kit. The histological slices were analysed by a digital image recognition software under a fully automated microscope and the rate of collagen I was converted into amounts of grey tones.

Results

The amount of grey tones reached from 11.909 to 15.319 in the CCD-group, and from 2752 to 12.556 in the control group. The U-Test of Mann, Whitney and Wilcoxon for two independent samples generated a rank sum of 91,50 for CCD-patients, and of 79,50 for the control group. The Z-value was 3,246, the p-value 0,005. “Fisher`s exact test” identified a p-value of 0,0003.

Conclusions

The rate of collagen I in the oral mucosa seems to be increased significantly in CCD. This could explain the typical thick and fibrotic consistency of the gingiva and could be one reason for the delayed or missing dentition.     

Many Approved Drugs Have Bioactive Analogs With Different Target Annotations

Close structural relationships between approved drugs and bioactive compounds were systematically assessed using matched molecular pairs. For structural analogs of drugs, target information was assembled from ChEMBL and compared to drug targets reported in DrugBank. For many drugs, multiple analogs were identified that were active against different targets. Some of these additional targets were closely related to known drug targets while others were not. Surprising discrepancies between reported drug targets and targets of close structural analogs were often observed. On one hand, the results suggest that hypotheses concerning alternative drug targets can often be formulated on the basis of close structural relationships to bioactive compounds that are easily detectable. It is conceivable that such obvious structure–target relationships are frequently not considered (or might be overlooked) when compounds are developed with a focus on a primary target and a few related (or undesired) ones. On the other hand, our findings also raise questions concerning database content and drug repositioning efforts.