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Biomedical subjects

M Molteni

Publications and source records attributed to M Molteni.

At least 19 recordsLinked to original sources

Biological effect of the Planktothrix sp. FP1 cyanobacterial extract.

Cyanobacteria are common and potentially harmful inhabitants of freshwater and marine environments worldwide. Some waterbloom-forming cyanobacteria are toxic and they may cause animal death and adversely affect human health. A filamentous freshwater cyanobacterium, Planktothrix sp. FP1, was found to be responsible for a toxic algal bloom in Lake Varese (Italy) during August of 1997. In the present study, the biological effects of the Planktothrix sp. FP1 cell extract on Xenopus embryos and on human Peripheral Blood Mononuclear Cells (PBMC) were investigated. FETAX (Frog Embryo Teratogenesis Assay-Xenopus) showed that the cyanobacterial extract had no teratogenic potential, though embryotoxicity was detected (LC(50) 2.944g/l wet weight). The same extract inhibited the proliferation of PBMC stimulated in vitro by phytohemagglutinin (PHA), and strongly interfered with the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma).

Animals↗

Treatment of Helicobacter pylori infection. Indications and regimens: an update.

The management of Helicobacter pylori infection is still surrounded by controversy and uncertainties. Indications and correct application of current regimens for Helicobacter pylori infection are still considered a matter of debate. Regarding indications, only peptic ulcer and mucosa associated lymphoid tissue lymphoma are considered clear indications for treatment. In other conditions, such as atrophic gastritis, post gastric cancer resection, first-degree relatives of gastric cancer patients, dyspeptic patients, patients with gastro-oesophageal reflux disease and non-steroidal anti-inflammatory drug users, the value of Helicobacter pylori eradication is still controversial. The regimens for first-line and second-line treatment of Helicobacter pylori infection have been recommended by the Maastricht 2 Consensus Report. Although all the treatments are considered to be effective, physicians still do not agree on what first-line regimen should be used. Furthermore, a consensus on the duration of the antibiotic treatment is still lacking, although Maastricht guidelines for treatment of Helicobacter pylori infection recommend a one-week therapy. Also regimens, as a third-line treatment, and methods to improve compliance and clinical outcome are still a matter of debate. All these points will be considered in the present review

Amoxicillin↗

The gradient of visual attention in developmental dyslexia.

This study investigated the gradient of visual attention in 21 children, 11 children with specific reading disorder (SRD) or dyslexia and 10 children with normal reading skills. We recorded reaction times (RTs) at the onset of a small point along the horizontal axis in the two visual fields. In 70% of the cases the target appeared inside a circle acting as focusing cue and in 30% of the cases it appeared outside, allowing us to study the distribution of attentional resources outside the selected area. Normally reading children showed a normal symmetric distribution of attention. Indeed, RTs were directly proportional to the eccentricity of the target, and no visual field effect was observable. In contrast, children with SRD showed an anomalous and asymmetric distribution. The effect of the target eccentricity influenced RTs only when the stimulus was projected in the left visual field, whereas no effect was observable when the stimulus was projected in the right visual field. Findings allowed us to discuss the relation between this anomalous spatial distribution of visual attentional resources and dyslexia. To interpret the visual perceptual difficulties of children with SRD the hypothesis was made of a selective disorder of spatial attention (left inattention and right over-distractibility) related to a right parietal cortex dysfunction.

Adolescent↗

Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules.

Iloprost is a stable prostacyclin analog commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phenomenon (RP). Several mechanisms of action of the drug other than vasodilation and antiplatelet effect have been demonstrated that may be involved in the exertion of its clinical efficacy. Aim of the present study was to investigate whether iloprost down-regulated lymphocyte adhesion to endothelium through a modulation of adhesion molecule expression on the surface of endothelial cells. In the presence of iloprost, both lymphocyte adhesion and IL-1 stimulated expression of ICAM-1 and ELAM-1 exhibited a significant reduction, while unstimulated adhesion molecule expression was not significantly affected. Our results confirm that iloprost is able to down-regulate lymphocyte adhesion to endothelial cells and indicate that endothelium itself could be target of iloprost administration. Attenuation of the inflammatory response through modulation of cellular interactions could be suggested as a potential mechanism of action of iloprost, when used in the treatment of pathological conditions characterized by endothelial activation.

Cell Adhesion↗

Depressive symptoms as measured by the CDI in a population of northern Italian children.

The aim of this study was to evaluate some Children's Depression Inventory (CDI) psychometric properties and the prevalence of depressive symptoms in an unselected Italian sample of two hundred and eighty-four children aged 8 years. The CDI internal consistency was adequate (Cronbach's alpha:.80). The mean and standard deviation of CDI and the percentage of children at risk of depression (10.6%) in this sample are consistent with the figures reported by other studies carried out in northern Europe and North America. There were differences in gender and socioeconomic level in that boys scored higher than girls, and in the lower socioeconomic level there were more children at risk of depression. Ten items best discriminated children at risk for depression with 94% of correct classification. Most of these items consisted of observable signs. It is suggested that the CDI has noteworthy consistency across samples of relatively different cultures, that it can reliably be employed in the assessment of young children, and that observable signs outnumber internalizing symptoms of depression among children at risk

Catchment Area, Health↗

Discriminant validity of the Vineland Scales: score profiles of individuals with mental retardation and a specific disorder.

Utility of the Vineland Adaptive Behavior Scales-Expanded Form to discriminate among areas of adaptive behavior was substantiated by comparing profiles of scores obtained by three groups of individuals with mental retardation and either a communication, social behavior, or motor abilities disorder with those of matched individuals with mental retardation but no other disorder. Individuals with social behavior disorders obtained lower scores only in the Socialization domain; those with motor disorders, in the Motor domain and in the Personal and Domestic subscales that require motor competencies; and those with communication disorders, lower scores in the Communication domain and in the Community and Interpersonal Relationships subscales requiring expressive competencies. The utility of the Vineland Scales in obtaining an ecological evaluation of individuals with mental retardation is discussed.

Adult↗

Is attentional focusing an inhibitory process at distractor location?

This study investigated whether attentional focusing is an inhibitory mechanism of lateral distractor stimuli. Attentional focusing is defined as the visual system capacity to vary the spatial extent of the attended area without shifting attention. A two-choice-reaction time task with compatible and incompatible flankers was used. Results were interpreted on the basis of the time course of attentional focusing.

Adult↗

An open trial of paroxetine in the treatment of children and adolescents diagnosed with dysthymia.

This open-label study examined the potential efficacy of paroxetine in the treatment of children and adolescents diagnosed with dysthymia over a period of 3 months. Seven subjects were evaluated by the Hamilton Depression Rating Scale (HAM-D), by the Clinical Global Impression Severity of Illness Scale (CGI-S), and the Clinical Global Impression Improvement Scale (CGI-I). Seventy-one percent of patients had a satisfactory response, suggesting the efficacy of paroxetine in children with dysthymia.

Adolescent↗

Graves' disease: a host defense mechanism gone awry.

In this report we summarize evidence to support a model for the development of Graves' disease. The model suggests that Graves' disease is initiated by an insult to the thyrocyte in an individual with a normal immune system. The insult, infectious or otherwise, causes double strand DNA or RNA to enter the cytoplasm of the cell. This causes abnormal expression of major histocompatibility (MHC) class I as a dominant feature, but also aberrant expression of MHC class II, as well as changes in genes or gene products needed for the thyrocyte to become an antigen presenting cell (APC). These include increased expression of proteasome processing proteins (LMP2), transporters of antigen peptides (TAP), invariant chain (Ii), HLA-DM, and the co-stimulatory molecule, B7, as well as STAT and NF-kappaB activation. A critical factor in these changes is the loss of normal negative regulation of MHC class I, class II, and thyrotropin receptor (TSHR) gene expression, which is necessary to maintain self-tolerance during the normal changes in gene expression involved in hormonally-increased growth and function of the cell. Self-tolerance to the TSHR is maintained in normals because there is a population of CD8- cells which normally suppresses a population of CD4+ cells that can interact with the TSHR if thyrocytes become APCs. This is a host self-defense mechanism that we hypothesize leads to autoimmune disease in persons, for example, with a specific viral infection, a genetic predisposition, or even, possibly, a TSHR polymorphism. The model is suggested to be important to explain the development of other autoimmune diseases including systemic lupus or diabetes.

Animals↗

Endothelial tissue factor induction by T lymphocytes in systemic sclerosis.

We evaluated the ability of circulating T lymphocytes obtained from patients with systemic sclerosis (SSc) to induce the expression of tissue factor (TF) by human umbilical vein endothelial cells (HUVECs), and compared the results with those obtained from healthy controls. Nine patients with SSc and 10 sex- and age-matched healthy subjects were studied. Peripheral T lymphocytes obtained from SSc patients induced TF activity from HUVECs in a dose-dependent manner. A significant induction of endothelial TF was observed when 2 x 10(6) lymphocytes per well (TF values, mean+/-SD: 0.34+0.21U/microg of cell protein vs 0.04+/-0.03; n = 9, p = 0.001) or 1 x 10(6) lymphocytes per well (0.13+/-0.06 vs 0.04+/-0.04; n = 8, p<0.001) were added to HUVEC cultures. Lower concentrations of T lymphocytes were ineffective. Similar results were obtained with control lymphocytes. There were no differences in endothelial TF induction between patients and controls at any lymphocyte concentration tested. Within the SSc group, there were no correlations between TF activity and clinical features or disease duration.

Adult↗

Increased interferon-gamma (IFN-gamma) levels produced in vitro by alloactivated T lymphocytes in systemic sclerosis and Raynaud's phenomenon.

The aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-gamma compared with healthy controls. However, patients with clinically active disease had lower IFN-gamma levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-gamma than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4+ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-gamma. We suggest that T lymphocytes producing high levels of IFN-gamma might play a protective role in RP patients and in established scleroderma.

Adult↗

Effects of serotonin transporter promoter genotype on platelet serotonin transporter functionality in depressed children and adolescents.

OBJECTIVE: To investigate possible associations between serotonin transporter (5-HTT) promoter genotypic variants (l/l, l/s, and s/s) and differential regulation of platelet 5-HTT functionality parameters in a group of drug-naive depressed children and adolescents and healthy controls. METHOD: Children and adolescents with major depression (n = 18) defined by DSM-III-R criteria and normal controls (n = 21) were assessed both for platelet serotonin functionality and for genotypic variants on 5-HTT promoter region. Four parameters were considered: (1) serotonin uptake rate (Vmax); (2) serotonin dissociation constant (K(m)); (3) paroxetine binding and density of site (Bmax); and (4) paroxetine dissociation constant (Kd). RESULTS: Depressed children had lower Vmax and K(m). Control subjects with l/l genotype had significantly higher Vmax than control subjects with l/s and s/s genotype. Control subjects with l/l genotype also had significantly higher Vmax than their depressed homologs. In contrast, Vmax was not significantly different between depressed and nondepressed subjects who carried the other 2 genotypes. The 5-HTT promoter genotype, diagnoses, or their interaction had no effect on the other serotonin parameters. CONCLUSIONS: While showing a significant decrease of Vmax and K(m) in a group of drug-naive depressed children and adolescents, these data suggest that l/l genotype has a substantial effect on the decrease of Vmax during a depressive episode.

Adolescent↗

High frequency of T-cell lines responsive to immunodominant epitopes of thyrotropin receptor in healthy subjects.

In this study we analyzed the proliferative response to the extracellular domain of thyrotropin receptor (TSHR-ECD) of T-cell lines raised from healthy subjects. We found high frequencies of cell lines reactive to TSHR-ECD, ranging from 12% to 37%. The response of the cell lines to a set of overlapping peptides of TSHR-ECD showed that the most recognized epitopes by T lymphocytes are on the C-terminal portion. In particular, the regions of residues 360-396 and 258-277 are immunodominant in T-lymphocyte reactivity. A group of cell lines specific for the peptides of TSHR-ECD lost the response to the peptides during time in culture. However, these lines were still responsive to TSHR extracellular domain. The cloning of one of these lines showed three types of T-cell clones: (1) CD4+ clones (n = 4) highly responsive to the TSHR-ECD; (2) CD4+ clones (n = 4) low responsive to TSHR-ECD; (3) CD8+ clones (n = 9) not responsive to TSHR-ECD. The first group of clones was stable during time in culture, while the second group was characterized by the loss of the specific response to TSHR-ECD after some weeks from the first analysis. The observation of a spontaneous anergy in the second group of CD4+ clones suggests that mechanisms of control of the lymphocyte response to TSHR-ECD could be activated in vitro.

Adult↗

Differential effects of cyclo-oxygenase pathway metabolites on cytokine production by T lymphocytes.

Cyclo-oxygenase pathway metabolites released in the microenvironment by activated platelets and endothelial cells are potential local modulators of the immune response. In the present study, we have investigated the modulatory role of PGE2, iloprost (prostacyclin analogue), U-46619 (thromboxane analogue) on the release of IL-2, IFN-gamma, TNF-alpha and IL-6 by T lymphocytes. Our results show that PGE2 and prostacyclin differ in the regulation of cytokine production. PGE2 inhibited the release of IL-2 and IFN-gamma, while iloprost did not affect their production. The addition of PGE2 or iloprost greatly decreased the amount of TNF-alpha measured in the supernatants, although the rates of inhibition differed according to the kind of stimulation. Unlike that of PGE2, inhibition by iloprost was stronger in alloactivated cultures than in PHA-stimulated ones. In vitro IL-6 production was stimulated by PGE2 in alloactivated cultures and by iloprost, whatever the stimulus. These results are probably due to other cellular subsets contaminating the T-lymphocyte preparations. After complete removal of monocytes from cell cultures, there were inhibitory effects of lloprost and PGE2 on IL-6 released in the supernatants. We did not observe any significant effect of thromboxane analogue on the production of either cytokine.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Psychopathological disorders in a population of mentally retarded young adults.

Nosographic, clinical, therapeutic and psychosocial aspects of psychopathological disorders in 43 mentally retarded patients followed from 1988 to 1991 are presented. Mental problems in mentally retarded subjects are linked to mental illness but do not form a continuum with it. The prognosis is generally favourable. Great attention must be given to the psychosocial aspects as social integration is almost always at risk in the mentally retarded.

Adolescent↗