Using real-time fMRI to learn voluntary regulation of the anterior insula in the presence of threat-related stimuli

Previous studies have shown that healthy participants learn to control local brain activity with operant training by using real-time functional magnetic resonance imaging (rt-fMRI). Very little data exist, however, on the dynamics of interaction between critical brain regions during rt-fMRI-based training. Here, we examined self-regulation of stimulus-elicited insula activation and performed a psychophysiological interaction (PPI) analysis of real-time self-regulation data. During voluntary up-regulation of the left anterior insula in the presence of threat-related pictures, differential activations were observed in the ventrolateral prefrontal cortex, the frontal operculum, the middle cingulate cortex and the right insula. Down-regulation in comparison to no-regulation revealed additional activations in right superior temporal cortex, right inferior parietal cortex and right middle frontal cortex. There was a significant learning effect over sessions during up-regulation, documented by a significant improvement of anterior insula control over time. Connectivity analysis revealed that successful up-regulation of the activity in left anterior insula while viewing aversive pictures was directly modulated by dorsomedial and ventrolateral prefrontal cortex. Down-regulation of activity was more difficult to achieve and no learning effect was observed. More extensive training might be necessary for successful down-regulation. These findings illustrate the functional interactions between different brain areas during regulation of anterior insula activity in the presence of threat-related stimuli.     

Coronary angiogram and intervention through transulnar approach

BACKGROUND: This study was conducted to assess the safety and feasibility of a transulnar approach in performing diagnostic and interventional percutaneous coronary procedures. METHODS AND RESULTS: In the year 2004, a total of 100 patients underwent diagnostic angiography (n=64) and percutaneous coronary interventions (n=36) through transulnar approach. The patients' age ranged from 40 to 70 years and male to female ratio was 7.3:1. The cases of percutaneous coronary interventions were mostly elective procedures and emergency intervention was done in only 2 patients. The procedure was successful in 95 (95%) patients and unsuccessful in 5 (4 diagnostic and 1 percutaneous coronary intervention). The procedure was done through right ulnar artery in all except one patient in whom it was done through left ulnar artery. The total procedure time ranged between 25-45 min. Among the cases of percutaneous coronary interventions, single vessel angioplasty was performed in 23 (65.7%) patients, double vessel in 11 (31.4%) patients and triple vessel in 1 (3%) patient. All percutaneous coronary intervention patients received aspirin, clopidogrel and intravenous enoxaparin. Glycoprotein IIb/IIIa inhibitors were used in 7 patients. Complications such as local hematoma, ulnar artery perforation and reversible parasthesia occurred in one patient each. CONCLUSIONS: Tansulnar approach is a safe and easy alternative technique to perform diagnostic and therapeutic coronary interventions.     

Systolic contraction within aneurysmal rabbit myocardium following transplantation of autologous skeletal myoblasts

OBJECTIVE: Transplantation of autologous skeletal myoblasts (SKMB) into infarcted heart (or cellular cardiomyoplasty, CCM) augments myocardial performance in animal models of myocardial infarction. However, the effect of CCM in the setting of ventricular aneurysm has not been evaluated. This study analyzes the effects of transplanted SKMB on regional wall motion in a rabbit model of postinfarct ventricular aneurysm. We hypothesize that CCM, performed early after myocardial infarction, prevents the progression of dyskinetic wall motion. METHODS: Twenty-six rabbits underwent apical left ventricular cryoinfarction and soleus muscle biopsy for in vitro isolation of skeletal myoblasts. At 2 weeks postinfarct, the presence of ventricular aneurysm was detected in 23/26 animals by sonomicrometry and micromanometry. Seventeen of 23 animals were randomized to receive either 108 autologous myoblasts (CCM) or vehicle. Regional stroke work, percent systolic shortening, and synchronicity of regional wall motion were determined prior to, and four weeks following, injection (CCM; n = 9; vehicle, n = 8). Wall motion was evaluated under baseline and stress (dobutamine, 10 (g/kg/min) conditions. Six animals did not undergo randomization, but their hearts were used to measure the size of infarction. RESULTS: Four weeks following treatment of animals with ventricular aneurysm, systolic contractile activity was present in most animals treated with myoblasts but in none treated with vehicle (5/7 versus 0/6, respectively, P < 0.05). Dobutamine tended to accentuate the differences seen at baseline between the groups. CONCLUSIONS: This study demonstrates a high incidence of systolic contractile activity in a previously aneurysmal region of myocardium following CCM and may represent a novel therapy for the prevention and treatment of postinfarct aneurysm.     

Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method

The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 degrees C) the yield of the powder was 65+/-12% with 0.14+/-0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93+/-2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41+/-10%) and SEDS-processed budesonide without CD (61+/-3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.     

Muscarinic supersensitivity: A possible model for the sleep disturbance of primary depression?

The sleep changes induced in normal volunteers following the administration of scopolamine on 3 consecutive mornings resemble many of the abnormalities observed in the sleep of patients with primary depression: increased sleep latency and reduced rapid eye movement (REM) latency, total sleep time, and sleep efficiency. Furthermore, in a multivariate discriminant analysis--previously shown to distinguish the sleep records of depresed patients from those of normal controls and insomniac patients--the records from baseline nights were selected as normal and those after scopolamine as predominately depressed. Those observations suggest to us that muscarinic supersensitivity in normals may function as a pharmacological model for the sleep disturbances of depression.     

Physostigmine analgesia and somatosensory evoked responses in man.

14 normal volunteers were given 0.5 mg physostigmine or saline placebo i.v. in a randomized double blind trial. Subjects were pretreated with 0.5 mg methscopolamine i.m. on both days. Pain ratings and average evoked responses were obtained to brief electrical stimuli administered to the forearm. Pain response criterion was significantly higher on physostigmine than on placebo. Average evoked response component P100 was significantly smaller on physostigmine than placebo, especially for higher intensity stimuli. These results are consistent with central cholinergic modulation of pain and arousal systems in man.