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Biomedical subjects

A Guidotti

Publications and source records attributed to A Guidotti.

338 records · Page 19Linked to original sources

Sequelae of biochemical events following photochemical injury of rat sensory-motor cortex: mechanism of ganglioside protection.

In culture the protracted and abusive stimulation of glutamate (GLU) receptors results in neuronal death through a mechanism involving the persistent translocation of PKC and the destabilization of (Ca2+)i homeostasis [(Ca2+)i HD]. In contrast, intermittent GLU receptor use elicits a coordinated expression of immediate early genes (IEG) acting as nuclear third messenger. Brain ischemia also is known to result in the paroxysmal abusive stimulation of glutamate receptors. The glutamate receptive elements in turn degenerate largely as a function of their inability to control homeostatic Ca2+ due to the irreversible translocation of PKC. In the present study we employed an in vivo model of focal brain ischemia using the photosensitive dye, Rose bengal. With this model we sought to determine the neuroprotective actions of MK-801, a noncompetitive blocker of GLU at the NMDA-sensitive receptor and of the semisynthetic gangliosides LIGA 4 and LIGA 20 which in vitro have been demonstrated to block PKC translocation. Moreover, we sought to establish whether the persistent stimulation of ionotropic glutamate receptors would led to a change in ionotropic glutamate expression in the focal and perifocal area. Importantly, the perifocal area (i. e., the region surrounding the area of primary insult) is a region in which profound cellular reorganization occurs including neuronal death and glial proliferation and is a key region to target various neuroprotective drugs aimed at ameliorating the neurodegeneration following stroke. Receptor abuse dependent antagonists (RADA) drugs such as gangliosides selectively curtail the amplification steps that specifically differentiate signal transduction following physiological receptor use from that following pathological receptor abuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cellular and subcellular localization of an octadecaneuropeptide derived from diazepam binding inhibitor: immunohistochemical studies in the rat brain.

Immunocytochemical methods, both light and electron microscopic, were used to identify the cellular and subcellular locations of octadecaneuropeptide-like immunoreactivity (ODN-LI) in rat brains serially sectioned in total. ODN-LI includes a newly discovered family of rat brain neuropeptides that are processing products of a common endogenous neuropeptide precursor, diazepam binding inhibitor (DBI). The members of this neuropeptide family have been shown to displace benzodiazepines and beta carbolines from their specific recognition sites located on the allosteric modulatory centers of GABAA receptors. We have previously examined the distribution of DBI-LI in rat brain. The anti-ODN antiserum used in this study does not cross-react with rat DBI, and thus allows a distinct analysis of ODN-LI as opposed to DBI-LI, in rat brain. Neuronal perikarya with ODN-LI were located in many brain nuclei, such as the pontine n., reticular thalamic n., subgeniculate n., supraoptic n. and suprachiasmatic n., and also in brain areas such as cerebral and cerebellar cortex, hippocampus, inferior colliculus, olfactory bulb and subiculum. In addition to perikaryal labelling, a punctate or diffuse immunostaining with ODN antibodies was detected in many brain regions such as cerebellum, hippocampus, amygdaloid area, olfactory tubercle, some of the deep cerebellar nuclei and some circumventricular organs. At the electron microscopic level ODN-LI was identified in neuronal perikarya, processes and terminals. In the axon terminals, ODN-LI appears to be associated with synaptic vesicles. Whenever ODN-LI was detected within neurons, DBI-LI was also found in identical cells. In addition to neurons, DBI-LI was found in glia or glial-like cells, while ODN-LI was not found in these cells. Our findings are consistent with the hypothesis that ODN may be a neuron-specific processing product of DBI and that ODN-like peptides may act as putative endogenous allosteric modulators of various GABAA receptor subtypes.

Animals↗

Excitatory amino acid signal transduction in cerebellar cell cultures.

In primary cultures of cerebellar granule cells excitatory amino acid recognition sites are coupled with the stimulation of inositol phospholipid (PI) hydrolysis, cGMP formation and 45Ca2+ uptake. Mg2+, 2-amino-5-phosphonovalerate (APV) and phencyclidine (PCP) potently inhibit signal transduction in response to N-methyl-D-aspartate (NMDA), glutamate (GLU) and aspartate (ASP). Activation by quisqualate (QUIS) is transduced selectively into stimulation of PI hydrolysis and this response is not sensitive to inhibition by Mg2+, APV and PCP. Activation by kainate (KA) is transduced into potent stimulation of cGMP formation and 45Ca2+ uptake. Transduction of KA signal is not affected by Mg2+ and is relatively insensitive to PCP and APV.

Amino Acids↗

[Thoracic radiography. Comparison of asymmetric screen-film, technic of mechanical homogenization, and conventional technics].

This study was aimed at comparing three different systems, i.e., asymmetric screen-film, mechanical homogenized and conventional techniques, in standing frontal and lateral plain radiographs of the chest. Two hundred consecutive patients with normal posteroanterior (PA) and lateral films were randomly subdivided into 4 groups. Each group was submitted to chest radiographs with a different technique: asymmetric screen-film systems (InSight HC and High Light GCA), mechanical homogenized (Tau-Gil Homogenized) and conventional high-kilovoltage techniques. The exposure values for frontal projections ranged 110 kV (InSight HC) to 141 kV (Tau-Gil), while for lateral projections they ranged 123 kV (conventional technique) to 143 kV (Tau-Gil). Statistically significant differences were observed between the two asymmetric systems as regards exposure values, High Light exhibiting higher mean values in the frontal projection (t-test p < 0.05). Image quality was studied jointly by 3 experienced chest radiologists. The observers were asked to grade, on a 3-point ordinal scale, the conspicuity of mediastinal borders, of pulmonary vessels and of selected areas of lung parenchyma (i.e., retrocardiac, retrosternal and apical regions), as well as overall image quality on the frontal projection. The statistical analysis of paired differences was performed with the Mann-Whitney U-test. The asymmetric and the mechanical homogenized techniques were much better than the conventional technique in depicting tracheobronchial tree, retrocardiac parenchyma, azygos-esophageal recess and thoracic spine (p < 0.05). The mechanical homogenized system provided best overall image quality on frontal films, being superior to both InSight HC and conventional techniques, but not to the High Light GCA system; only the frontal projection obtained with the homogenized technique was compared, no filter being available for the lateral projection. When the two asymmetric systems were compared, the High Light system better depicted vascular structures on frontal films (p < 0.05), while apical areas were better demonstrated with the InSight system, namely with lateral films (p < 0.05).

Female↗

[Bedside thoracic radiography: a comparison between 3 different types of grid].

Bedside chest radiography accounts for an increasingly large portion of all chest X-ray examinations. Nevertheless, image quality is often poor mainly because of scattered radiations which decrease image contrast. Moreover, usually no grid is employed because of difficult beam alignment. This work was aimed at comparing different radiologic grids for bedside chest radiography. Fifty patients submitted to two bedside chest radiographs in 24 hours were studied. All the patients underwent the first exam with a Kodak InSight cassette with a newly-designed (columnar type) grid inside, while the second exam was performed with a conventional 8:1 focused lead-strip grid (Gilardoni) in 25 patients and with a 6:1 focused lead-strip grid (Gilardoni) in the extant 25 patients. Both grids were assembled in a Kodak InSight radiographic cassette. Three independent radiologists evaluated film quality, focusing on the depiction of some anatomical structures--e.g., the tracheobronchial tree, the retrocardiac lung, and devices. Seventy-five examinations were obtained for each grid and for each evaluated structure and graded as "good", "acceptable" and "poor". In the 6:1 vs columnar grid test, the highest rate of "good" and "acceptable"--i.e., diagnostic--findings was observed with the columnar grid in evaluating pulmonary vessels (71/75); the highest rate of "poor" findings was obtained with the same grid in evaluating tracheal bifurcation (43/75). In the 8:1 vs columnar grid test, the highest rate of diagnostic findings was shown by the conventional grid in evaluating retrocardiac lung parenchyma and by the columnar grid for pulmonary vessels (69/75); the highest rate of "poor" findings was obtained with the columnar grid in evaluating tracheal bifurcation (40/75). The statistical analysis of the results (Wilcoxon test) was made to compare the two conventional grids with the new columnar one. Statistically significant differences were observed between the 8:1 grid and the columnar grid to evaluate the bronchial tree. No differences were observed between the 8:1 grid and the columnar grid. Furthermore, to determine the effects of different degrees of grid decentering on image quality, a series of exposures was made using a lung-chest phantom. The grids, both the lead-stripe and the columnar one, were comparable. The higher-ratio grid proved better in evaluating tiny details. The columnar grid exhibited better tolerance to X-ray beam and to grid decentering.

Equipment Design↗

Pulmonary embolism: the role of computed tomography and magnetic resonance imaging.

The technological progress in Computed Tomography (CT) (spiral and electron beam) and Magnetic Resonance Imaging (MRI fast sequences) has stimulated their interest in the diagnosis of acute and chronic pulmonary embolism (PE). They are noninvasive procedures able to identify thrombi up to the level of segmental pulmonary branches. This result, albeit not ideal, is significant, in view of the lower clinical relevance of peripheral emboli as compared to more central locations, especially in the absence of peripheral venous thrombosis. Spiral CT allows satisfactory assessment of pulmonary branches with high sensitivity (65-100%), specificity (89-96%), positive predictive value (95%) and negative predictive value (80-100%) in the diagnosis of PE. MRI with spin-echo sequences has also a satisfactory sensitivity (75-90%), specificity (up to 100%), positive predictive value (86%) and negative predictive value (85%). Recently, MR angiography was shown to be able to depict smaller pulmonary branches (6th and 7th generation), even if its efficacy in the identification of emboli has not been demonstrated as yet. CT and MRI are bound to play an increasingly relevant role in the diagnosis of PE.

Humans↗