Biomedical subjects

L Guidi

Publications and source records attributed to L Guidi.

At least 19 recordsLinked to original sources

PubMed2004

Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment.

OBJECTIVE: To assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Conventional MR was acquired in 41 patients with RR MS and 16 demographically matched normal control subjects (NCs). An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and neuropsychological scores was assessed. RESULTS: Neuropsychological assessment allowed for the identification of 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS sample showed lower values of normalized cortical volumes (NCVs) than did the NC group (p = 0.01). Upon grouping of MS patients according to cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs. Moreover, there were positive correlations between NCV values and measures of verbal memory (r = 0.51, p = 0.02), verbal fluency (r = 0.51, p = 0.01), and attention/concentration (r = 0.65, p < 0.001) in MS-ci patients. Furthermore, NCV values were decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the neuropsychological measures correlated to NCV values in the MS-cp patient group. CONCLUSIONS: Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Adult↗

PubMed2004

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Adolescent↗

PubMed2004

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis.

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Adolescent↗

PubMed2003

Evidence of early cortical atrophy in MS: relevance to white matter changes and disability.

OBJECTIVE: To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing-remitting (RR) and primary progressive (PP) forms of the disease. METHODS: Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed. RESULTS: Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration (<5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal brain lesion volume (<5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS). Measures of NCV in individual patients were negatively correlated with T2-weighted lesion volume (r = -0.47, p < 0.001) and disease duration (r = -0.25, p < 0.05) only in the patients with RR MS. NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = -0.64, p < 0.0001) than for RR (r = -0.27, p = 0.04) MS patients. CONCLUSIONS: These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.

Adolescent↗

PubMed2003

Imaging neuronal and axonal degeneration in multiple sclerosis.

Neuronal and axonal damage has become an important issue in multiple sclerosis. This has been emphasised by recent magnetic resonance imaging (MRI) studies that have shown evidence of axonal damage in both lesional and non-lesional white matter and in grey matter. In this respect, proton MR spectroscopy (by monitoring levels of Nacetylaspartate, a putative marker of axonal integrity) and computed measurements of cerebral volumes have been particularly illuminating. Recent studies using these MRI measures have demonstrated that cerebral neuro-axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of neuronal pathology in the pathogenesis of the disease should be given due importance and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards neuronal protection.

Aspartic Acid↗

PubMed2003

Interleukin-6 release in the hepatic blood outflow during normothermic liver ischaemia in humans.

BACKGROUND: Liver surgery techniques have consistently improved and normothermic ischaemia of the liver is considered to be a safe procedure to reduce intraoperative haemorrhage. Hepatic failure, however, remains a significant complication. In liver ischaemia-reperfusion injury, cytokines play a key proinflammatory role. Cytokines may be part of the intercellular signalling that leads to recovery or to failure after major surgery. Moreover, they could be potential predictors of the outcome. Modulation of the pattern of cytokine response in the early postsurgery period could represent a new approach to minimise the impact of these procedures. AIMS: The aim of our study was to analyse the cytokine pattern in the hepatic blood outflow in patients undergoing surgical intervention of partial liver resection with clamping of the hepatic pedicle and liver ischaemia, and to correlate the cytokine behaviour with clinical parameters. PATIENTS: We studied eight patients (mean age 55 years) who underwent surgical intervention of liver resection during vascular exclusion of the hepatic pedicle. Patients were monitored for haemodynamic and haematological parameters during the pre-, infra- and postoperative period. METHODS: IL-I alpha, IL-6, TNF-alpha and IFN-gamma were assayed from peripheral and central vein blood at different times. Blood samples for cytokine assays were also drawn from the supra-hepatic veins after clamping of the porta hepatis. RESULTS: We found a significant increase of the IL-6 levels in the supra-hepatic samples during liver ischaemia, while the trend with IL-1alpha was less clear; IFN-gamma and TNF-alpha were undetectable with the methods used. IL-6 levels appeared to correlate positively with bilirubin and gamma-GT levels and negatively with the degree of acidosis. CONCLUSIONS: Our study confirms that during surgical ischaemic stress there is an increase of IL-6 serum levels more relevant in supra-hepatic vein blood. Cytokines could contribute to modulate the inflammatory response to liver ischaemia.

Adult↗

PubMed2003

An update on the medical treatment of Crohn's disease.

Crohn's disease (CD) is a chronic transmural inflammation that may involve any part of the alimentary tract. The affected patients show peculiar metabolic characteristics; they often have a reduced body weight, due to reduction of lipid stores (in spite of lean mass depletion) and an increased utilization of lipids as fuel substrate. An alteration of nutritional status, up to real malnutrition, is common in CD and malnutrition's effects influence the course of disease, acting as independent factors. We will give a description of the main pharmacological approaches in CD management; the first line therapy for CD patients remains the combinations of aminosalicylates, antibiotics, corticosteroids and immunomodulatory agents. The development of new biological agents for the treatment of inflammatory bowel diseases has added to the growing armamentarium of available therapy. We also will explain the importance of enteral nutrition, whose importance goes over the simple amelioration of nutritional status, especially in childhood CD, where it has shown to be as effective as traditional therapy.

Adjuvants, Immunologic↗

PubMed2001

Glucose-6-phosphate dehydrogenase supports the functioning of the synapses in rat cerebellar cortex.

This study investigates heterogeneous glucose-6-phosphate dehydrogenase (G6PD) expression in the rat cerebellar cortex. G6PD activity and its electrophoretic pattern, evaluated on the cerebellar homogenate, were found to be similar to those of other brain areas. However, histochemical and immunohistochemical analyses revealed that the highest expression of G6PD activity and protein was in Purkinje's cells, followed by the molecular and granular layers. Electron microscopy analysis showed that, in Purkinje's cells, the G6PD reaction products were concentrated in the neurites while in the basket cells in the cell body. The granules showed a weaker activity everywhere. The quantitative distribution of G6PD is discussed in the light of the neurochemical function of these cells.

Animals↗

PubMed2001

Correlates of MS disability assessed in vivo using aggregates of MR quantities.

OBJECTIVES: To assess the magnitude of the correlations between disability and composite MRI scores in patients with MS. METHODS: T2- and T1-weighted MRI, magnetization transfer imaging, diffusion tensor imaging, and MRS imaging scans of the brain from 23 patients with MS were obtained. T2 lesion volume, T1 lesion volume, brain magnetization transfer ratio, average brain diffusivity (D), and brain N-acetylaspartate/creatine ratio were measured. RESULTS: The correlations between the Expanded Disability Status Scale (EDSS) score and each of the MR quantities taken in isolation were not significant, with the exception of the correlation between EDSS and the NAA/creatine ratio (r = -0.50; p = 0.01). In contrast, three of the composite MR scores computed using regression models were strongly correlated with the EDSS scores (r range, 0.58 to 0.73; p range, 0.004 to 0.0001). The model that included T2 and T1 lesion volumes and brain D explained 34% of the EDSS variance; the model that included T2 and T1 lesion volumes and brain N-acetylaspartate/creatine ratio explained 36% of the EDSS variance; the model that included T1 lesion volume, brain D, and brain N-acetylaspartate/creatine ratio explained 53% of the EDSS variance. CONCLUSIONS: The results suggest that multiparametric MR models have the potential to provide powerful measures to monitor MS evolution.

Adult↗

PubMed2001

Effect of chronic ozone fumigation on the photosynthetic process of poplar clones showing different sensitivity.

Rooted cuttings from two poplar clones (Populus x euramericana, I-214, and Populus deltoides x maximowiczii, Eridano) were exposed for 15 days to diurnal square-wave treatment with ozone (60 nL L-1 for 5 h day-1). Completely fully expanded leaves exposed to ozone showed a reduction in net CO2 assimilation rate as compared to the control leaves during whole exposure period in both the clones. The reduction was related to a strong stomatal closure in clone I-214, but also to an altered mesophyll activity ascribed to limitation of the dark reactions of photosynthetic process. The results obtained in leaves of I-214 subjected to long-term fumigation seem to support the view that the decrease in quantum yield of electron transport may be a mechanism to down-regulate photosynthetic electron transport so that production of ATP and NADPH would be in equilibrium with the decreased demand in the Calvin cycle. In Eridano the CO2 assimilation was reduced because of the exposure and any alteration in stomatal conductance was observed. Thus, chlorophyll fluorescence parameters showed that an inhibition of photosystem II had occurred (reduction in Fv/Fm ratio), while no alterations in quenching parameters were observed upon illumination. The results seem to indicate that an alternative sink for reducing equivalent, other than carbon metabolism is present.

Adenosine Triphosphate↗

PubMed2001

Role of DNA-dependent protein kinase in recognition of radiation-induced DNA damage in human peripheral blood mononuclear cells.

The DNA-dependent protein kinase (DNA-PK) complex plays a crucial role in radiation-induced DNA damage recognition. The complex includes the ku heterodimer, which comprises ku 70 and ku 80 subunits, that binds DNA termini of breaks without sequence specificity, and the catalytic subunit DNA-PKCS: The activation of the DNA-PK complex was studied in X-irradiated peripheral blood mononuclear cells (PBMC) from subjects of different ages. Radiation-induced changes in the DNA-binding activity of the ku heterodimer, and in the concentrations of ku 70, ku 80, DNA-PKcs and phosphorylated ku 80 were determined in nuclear and cytoplasmic extracts. DNA-binding activity was increased by irradiation only in the nuclear extract of PBMC from young, but not from elderly subjects, whereas it was found unchanged in cytoplasmic extracts regardless of age. The radiation-induced activation of the DNA-PK complex may result from the increased concentrations of ku 80 and DNA-PKcs in the cytoplasm of PBMC from young, but not from elderly subjects, leading to a higher concentration of phosphorylated ku 80 which readily migrates to the nucleus where, after dimerization with ku 70, binds to DNA breaks. These findings suggest major steps involved in DNA-PK activation, and the intracellular and molecular changes that may account for the age-dependent impairment of DNA repair capacity in irradiated mammalian cells.

Adult↗

PubMed2000

Modulation of X-ray-induced damage recognition and repair in ageing human peripheral blood mononuclear cells by an interleukin-6-type cytokine.

We have investigated the effects of an interleukin (IL)-6-type cytokine on the DNA-binding activity of ku and on unscheduled DNA repair in X-ray-treated peripheral blood mononuclear cells (PBMC) from human subjects of different ages. The cytokine used, called K-7/D-6, is an IL-6 variant with increased in vivo and in vitro biological activity compared to the wild type molecule. Ku is the DNA-binding component of the DNA-dependent protein kinase (DNA-PK). It binds the ends of various types of DNA discontinuity and is involved in the repair of DNA breaks caused by V(D)J recombination, isotype switching, physiological oxidation reactions, ionizing radiation and some chemotherapeutic drugs. The ku-dependent repair process, called non-homologous end joining, is the main DNA double strand break repair mechanism in irradiated mammalian cells. Results show that K-7/D-6 significantly increases DNA-binding activity of ku in irradiated PBMC from young but not from elderly subjects. However, K-7/D-6 is able to induce unscheduled DNA repair in irradiated PBMC from both young and elderly subjects. These effects of K-7/D-6 are relevant to the mechanisms of the cellular response to DNA damage.

Adult↗

PubMed2000

Imaging axonal damage in multiple sclerosis by means of MR spectroscopy.

Axonal damage in multiple sclerosis has become an important issue. This has been emphasized by recent in vivo proton magnetic resonance (MR) spectroscopy and in vitro pathology studies that have found axonal damage in both lesions and the surrounding normal-appearing white matter. In particular, proton MR spectroscopy, by monitoring levels of N-acetylaspartate (a putative marker of axonal integrity), has been particularly illuminating, as the extent of axonal injury associated with white matter inflammation and demyelination had not been well appreciated from classical pathology studies. Recent MR data demonstrate that cerebral axonal damage begins and contributes to disability from the earliest stages of the disease. This implies that the apparently primary role of axonal damage and loss in the pathogenesis of the disease should be given due importance, and argues for the early treatment of multiple sclerosis with agents directed not only against inflammation, but also towards axonal protection.

Animals↗

PubMed2000

Screening of bean cultivars for their response to ozone as evaluated by visible symptoms and leaf chlorophyll fluorescence.

Fourteen Italian cultivars of Phaseolus vulgaris were exposed to a single pulse of ozone (O(3), 150 nl l(-1)) or to filtered air (<3 nl l(-1)) for 3.5 h. O(3) sensitivity was assessed by recording the extent of visible symptoms, effects on chlorophyll (Chl) content and changes in Chl a fluorescence parameters. This paper reports the results of an initial screening of 14 bean cultivars that was used to select a small number of cultivars for further work. Seven cultivars showed visible symptoms of injury in the range of 2-60 h after the end of the O(3) fumigation. O(3) significantly depressed total Chl content in most cultivars and a significant correlation was found between Chl content and visible symptoms. Most cultivars showed a significant change in the F(v)/F(m) ratio, even when there were no visual symptoms. There was no relationship between the extent of visual symptoms and quenching coefficients, indicating that these parameters were of no use in the determination of sensitivity to O(3) stress.

Journal Article↗

PubMed2000

Cytochemical and immunocytochemical methods for electron microscopic detection of glucose-6-phosphate dehydrogenase in brain areas.

This paper reports on protocols for the cytochemical and immunocytochemical determination of the glucose-6-phosphate dehydrogenase (G6PD) in brain areas by electron microscopy (EM). The cytochemical assay consists of a pre-embedding staining of small and flat tissue blocks, which were first mildly fixed and then floated in a staining mixture based on the reduction of tetrazolium salts by NADPH. Tissue blocks were then washed, post-fixed in OsO(4), dehydrated through graded ethanol concentrations and embedded in resin. Ultrathin sections were then obtained and observed at the EM. The immunocytochemical technique was performed on completely fixed tissues of perfused animals. After the tissue embedding in resin, ultrathin sections were obtained and treated with a primary anti-erythrocyte G6PD antibody, produced and purified in our laboratory. The immunostaining was performed with secondary gold-conjugated antibody. Gold grains were well evident by EM analysis thus revealing the G6PD protein in the subcellular compartments. These protocols are useful to detect peculiar populations of neurons which express high levels of G6PD to sustain processes of neural plasticity in some brain areas.

Animals↗

PubMed2000

Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Adult↗

PubMed2000

Cerebellar deficit and respiratory impairment: a strong association in multiple sclerosis?

The aim of the study was to analyse pulmonary function and to identify reliable prognostic factors associated with respiratory abnormalities in a consecutive series of patients with multiple sclerosis (MS). Pulmonary function was evaluated by means of a battery of measures, including maximal voluntary ventilation, forced vital capacity, forced expiratory volume, in 71 consecutive patients with primary and secondary progressive MS. Respiratory impairment was common in MS patients, occurring in 63.4% of all patients, ranging from 82.9% in non-ambulatory patients (with EDSS score >6.5) to 35.7% in ambulatory patients (with EDSS score <6). Severity of illness and cerebellar and mental impairment were significantly negatively associated with basal pulmonary function. Coordination plays an important role in determining respiratory abnormalities: respiratory abnormalities were found in 27 out of 32 patients (84.4%) with severe cerebellar impairment. The presence of severe cerebellar signs was associated with a very high risk of occurrence of respiratory impairment (O.R. = 6.24; 95% C.I. 1.71-22.82). Other significant variables were severity of illness (EDSS score > 6.5) (O.R. =4.71; 95% C.I. 1.42-15.66) and long disease duration (> 15 years) (O.R. = 3.39; 95% C.I. 1.01-11.42).

Analysis of Variance↗

PubMed1999

High glucose-6-phosphate dehydrogenase activity contributes to the structural plasticity of periglomerular cells in the olfactory bulb of adult rats.

Glucose-6-phosphate dehydrogenase (G6PD) activity, assayed spectrophotometrically, was found to be higher in the olfactory bulb (OB) than in other brain areas of adult rats [P. Ninfali, G. Aluigi, W. Balduini, A. Pompella, Glucose-6-phosphate dehydrogenase is higher in the olfactory bulb than into other brain areas, Brain Res. 744 (1997) 138-142]. Histochemical demonstration of G6PD activity in cryostat sections of OB, analyzed with optical microscopy, revealed a marked and well defined line of formazan deposition in the internal part of the glomerular layer (Glm), indicating that G6PD was much higher in cells distributed along the glomeruli. Electron microscope analysis showed that G6PD activity was mainly concentrated in cytoplasm and dendrites of periglomerular cells, the interneurons which span glomeruli and connect olfactory nerves with mitral/tufted cells. Since G6PD regulates the flux through the hexose monophosphate shunt (HMS) pathway, which provides NADPH for reductive biosynthesis and pentose phosphates for nucleic acid formation, it can be concluded that high G6PD activity in periglomerular neurons is functional to their differentiating capability. This result is consistent with the occurrence of structural plasticity events in the OB of adult rats.

Animals↗