Cortical activation to voluntary movement in amyotrophic lateral sclerosis is related to corticospinal damage: electrophysiological evidence.

OBJECTIVES: The time course of mu and beta sensorimotor rhythms, with event-related desynchronisation (ERD) to preparation and execution of voluntary movement followed by synchronisation (ERS) after movement, is considered to indicate cortical activation and idling, respectively. We investigated ERD and ERS in amyotrophic lateral sclerosis (ALS) patients and the relationship with anatomical and neurophysiological measures of corticospinal tract damage. METHODS: Pre-movement mu and beta ERD, and post-movement beta ERS were analysed in 16 ALS patients and 15 healthy controls performing self-paced brisk right thumb extensions. Apparent diffusion coefficient (ADC) of corticospinal tract was measured with magnetic resonance imaging (MRI). Motor-evoked potentials (MEPs) to the right abductor pollicis brevis were obtained using transcranial magnetic stimulation (TMS). RESULTS: Movement-related electromyographic activity was similar in the two groups. Post-movement ERS was significantly reduced in ALS group and negatively correlated with the amount of corticospinal damage as from MRI and TMS measures. ERD did not significantly differ between groups. CONCLUSIONS: Alterations of cortical activity in ALS patients were limited to the post-movement phase, as indicated by reduced ERS, and could be linked to reduced cortical inhibition rather than to generalised hyperexcitability. SIGNIFICANCE: The correlation between ERS and corticospinal damage severity might be interpreted as a functional compensation or dysfunction of inhibitory systems paralleling corticospinal damage.

Diabetes regulates mitochondrial biogenesis and fission in mouse neurons.

AIMS/HYPOTHESIS: Normal mitochondrial activity is a critical component of neuronal metabolism and function. Disruption of mitochondrial activity by altered mitochondrial fission and fusion is the root cause of both neurodegenerative disorders and Charcot-Marie-Tooth type 2A inherited neuropathy. This study addressed the role of mitochondrial fission in the pathogenesis of diabetic neuropathy. METHODS: Mitochondrial biogenesis and fission were assayed in both in vivo and in vitro models of diabetic neuropathy. Gene, protein, mitochondrial DNA and ultrastructural analyses were used to assess mitochondrial biogenesis and fission. RESULTS: There was greater mitochondrial biogenesis in dorsal root ganglion neurons from diabetic compared with non-diabetic mice. An essential step in mitochondrial biogenesis is mitochondrial fission, regulated by the mitochondrial fission protein dynamin-related protein 1 (DRP1). Evaluation of diabetic neurons in vivo indicated small, fragmented mitochondria, suggesting increased fission. In vitro studies revealed that short-term hyperglycaemic exposure increased levels of DRP1 protein. The influence of hyperglycaemia-mediated mitochondrial fission on cell viability was evaluated by knockdown of Drp1 (also known as Dnm1l). Knockdown of Drp1 resulted in decreased susceptibility to hyperglycaemic damage. CONCLUSIONS/INTERPRETATION: We propose that: (1) mitochondria undergo biogenesis in response to hyperglycaemia, but the increased biogenesis is insufficient to accommodate the metabolic load; (2) hyperglycaemia causes an excess of mitochondrial fission, creating small, damaged mitochondria; and (3) reduction of aberrant mitochondrial fission increases neuronal survival and indicates an important role for the fission-fusion equilibrium in the pathogenesis of diabetic neuropathy.

Diagnostic accuracy of CT colonography in patients with positive faecal occult blood test: results of the Italian project Legatumori 2003-2006.

PURPOSE: In the framework of the 3-year project of the Italian Legatumori (2003-2006), we evaluated the diagnostic accuracy of computed tomography (CT) colonography in detecting colorectal lesions in a screening population with positive faecal occult blood test (FOBT). MATERIALS AND METHODS: Two hundred and thirty asymptomatic subjects (age range 45-80 years) were enrolled in the study. CT colonography was performed with standard patient preparation (no faecal tagging) and a 4-detector-row CT scanner. Image analysis was carried out with primary 2D analysis and the use of 3D endoluminal views to solve difficult cases. Patients were referred for conventional colonoscopy in the following situations: detection of three or more suspected lesions with maximum diameter6 mm; presence of colonic masses (maximum diameter>3 cm). RESULTS: CT colonography detected colonic masses in 12 out of 135 subjects (8%). It generated 93 false positives and 19 false negatives in the identification of diminutive lesions (6 mm. Sensitivity was 83% in smaller lesions and 93% in lesions>6 mm; specificity was 45% and 59%, respectively. CONCLUSIONS: In a screening population with positive FOBT, CT colonography without faecal tagging and no definite size threshold for the reporting of polyps showed very low specificity but high sensitivity in the detection of all colorectal lesions.

Performance evolution of hydrophobic treatments for stone conservation investigated by MRI.

1H-MRI has been applied to the evaluation of the performances of a hydrophobic polymer (Paraloid B72), widely used for the conservation of monumental buildings and other stone artifacts. By this technique it has been possible to visualize the water diffusion in a treated rock material (Pietra di Lecce, a highly porous Italian biocalcarenite) and then indirectly the spatial distribution of the polymer in the rock. The effects of wetting-drying cycles on the hydrophobic efficacy of the acrylic polymer in the inner layers of the rock were also studied. A notable decrease in the water-repellence inside the stone was detected and attributed to a loss of adhesion of the polymer to the substrate, promoted by the action of water.

Involvement of protein kinase C in the response of Neurospora crassa to blue light.

As a first step towards understanding the process of blue light perception, and the signal transduction mechanisms involved, in Neurospora crassa we have used a pharmacological approach to screen a wide range of second messengers and chemical compounds known to interfere with the activity of well-known signal transducing molecules in vivo. We tested the influence of these compounds on the induction of the al-3 gene, a key step in light-induced carotenoid biosynthesis. This approach has implicated protein kinase C (PKC) as a component of the light transduction machinery. The conclusion is based on the effects of specific inhibitors (calphostin C and chelerythrine chloride) and activators of PKC (1,2-dihexanoyl-sn-glycerol). During vegetative growth PKC may be responsible for desensitization to light because inhibitors of the enzyme cause an increase in the total amount of mRNA transcribed after illumination. PKC is therefore proposed here to be an important regulator of transduction of the blue light signal, and may act through modification of the protein White Collar-1, which we show to be a substrate for PKC in N. crassa.

Comparison between the suppressive effects of dexamethasone and loperamide on cortisol and ACTH secretion in some pathological conditions.

Since in patients with Cushing's disease, unlike in normal subjects, tonic inhibitory opioid control of ACTH secretion does not operate, use of the opiate agonist loperamide (LOP) has recently been proposed in the diagnosis of hypercortisolemic states. We compared the sensitivity, specificity and diagnostic accuracy of the LOP test (16 mg orally) with corresponding results of the dexamethasone test (DXM, 1 mg orally overnight) in 23 normal subjects and in a total of 42 patients, affected by Cushing's disease (n = 8), incidentally discovered adrenal masses with impaired function of the hypothalamic-pituitary-adrenal (HPA) axis (n = 6), obesity (n = 21) and depression (n = 7). While in controls both DXM and LOP strongly suppressed plasma cortisol and ACTH, in Cushing's disease and in incidentalomas no patient showed a decrease in cortisol levels below 50 ng/ml or a reduction in plasma cortisol greater than 50% of basal values in response to LOP and DXM. In obese subjects both drugs significantly reduced plasma cortisol and ACTH without giving false positive results. In the depressed group only 3/7 patients showed a decrement in cortisol levels below 50 ng/ml after LOP in contrast to 6/7 after DXM. Thus, in patients with impairment of the HPA-axis, i.e. in Cushing's disease and in patients with adrenal incidentalomas and hormonal abnormalities, LOP and DXM test sensitivity was 100%. In controls and in obese patients specificity was 100% both with LOP and DXM, while in depressed patients it was 43% and 86% with LOP and DXM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of erythropoietin administration on prolactin secretion in normal subjects.

To evaluate the acute effect of human erythropoietin (r-HuEPO) on basal and stimulated prolactin (PRL) secretion, 18 normal subjects (12 females, 6 males) were studied. The PRL response to thyrotropin-releasing hormone (TRH; 200 micrograms intravenously, n = 7), metoclopramide (MCP, 20 mg intravenously, n = 5) and fenfluramine (FF, 60 mg os, n = 6) was tested in presence of saline or r-HuEPO (30 U/kg intravenously). The drug neither modified basal PRL levels nor affected the normal PRL release to TRH, MCP and FF. Our results indicate that, in normal subjects, the acute administration of therapeutic doses of r-HuEPO does not interfere with PRL secretion both after a direct pituitary stimulus and after stimuli involving dopaminergic and serotoninergic pathways.