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Biomedical subjects

G Mancuso

Publications and source records attributed to G Mancuso.

At least 37 records · Page 2Linked to original sources

Effects of nicotine administered via a transdermal delivery system on vigilance: a repeated measure study.

Fifteen 18- to 25-year-old male smokers were tested in a within-subjects design to determine the influence of a transdermal patch of 21 mg nicotine on vigilance. Subjects were tested on the RVIP test (Rapid Visual Information Processing test) 1.30, 3.00 and 6.30 h after patch application, to verify the involvement of the dose of nicotine on the performance. This study confirms and extends the increasing effects of nicotine on vigilance previously found with orally and transdermally given nicotine. Moreover, it showed that such performance was independent of the time of nicotine absorption (1.30, 3.00 and 6.30 h after patch application), which suggests that a relatively low dose of nicotine suffices to activate vigilance processing. Regarding motor performance, no convincing effect of nicotine was observed on reaction time.

Administration, Cutaneous↗

Selective effects of nicotine on attentional processes.

RATIONALE: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect of nicotine or by a reversal effect of a nicotine-induced, abstinence deficit. In addition, there is dispute about the cognitive processes underlying the changes in performance. METHODS: This study has approached the first question by using the nicotine patch, in order to administer nicotine chronically. In addition, we examined the effects of nicotine on attention with a selection of tests which assessed the intensity and selectivity features of attention, using the Random Letter Generation test, the Flexibility of Attention test and the Stroop test. RESULTS: Nicotine enhanced the speed of number generation and the speed of processing in both the control and interference conditions of the Stroop test. There were no effects on attentional switching of the Flexibility of Attention test. CONCLUSION: The results are consistent with the hypothesis that nicotine mainly improves the intensity feature of attention, rather than the selectivity feature.

Adolescent↗

Long-lasting allergic patch test reactions: a study of patients with positive standard patch tests.

The purpose of this study was to determine the duration of patch test reactions and the frequency of long-lasting allergic patch test reactions (LLAPTR), and to identify the possible factors related to the development of the LLAPTR. For this purpose, a group of 263 patients positive to 1 or more allergens in the GIRDCA standard series was recruited. Readings were made for each patient 2 and 3 days after patch test application and continued every 2nd and 3rd day until the disappearance of all palpable erythema. The % of LLAPTR out of the total of reactions was high: 17.9%). Kathon CG was the hapten that caused LLAPTR most frequently, with 16 cases, a frequency of 76.1%), and a mean duration of the patch test reactions of 25.4 days. Risk factors investigated were age, sex, atopy, intensity of the patch test reaction and sensitivity to some allergens with the greatest number of positive patch tests. The relative importance of each risk factor was calculated by multivariate stepwise logistic regression analysis. It was found that a Kathon CG sensitivity was the most important risk factor for LLAPTR. 2nd was atopy, followed by strong patch test reaction. Rejected risk factors were sex, age and sensitivity to nickel sulfate, potassium dichromate, Disperse Blue 124, fragrance mix and p-phenylenediamine.

Adult↗

Tumor necrosis factor-alpha and virus expression in the central nervous system of cats infected with feline immunodeficiency virus.

Cytokine disregulation has been implicated in the pathogenesis of lentivirus-induced diseases. In the present study, 18 specific pathogen free (SPF) cats were inoculated with feline immunodeficiency virus (FIV) Petaluma strain and sacrificed at different times post-infection. Five additional SPF cats were used as controls. The cell localization of the cytokine tumor necrosis factor alpha (TNF-alpha) in the central nervous system (CNS) was determined by immunohistochemical and morphometric analyses with a polyclonal rabbit anti-human TNF-alpha antibody. TNF-alpha and FIV RNA were measured using competitive reverse transcriptase polymerase chain reaction (PCR) assays and the number of proviral genomes was estimated by competitive PCR. Portions of frontal cortex were collected from each animal and both formalin-fixed and snap-frozen and stored at -80 degrees C until used. The results showed that TNF-alpha is present mainly in astrocytes and microglial cells. Morphometric analysis showed that areas of TNF-alpha production increased in the early phases of infection. Molecular analyses demonstrated that the kinetics of proviral loads in the CNS were comparable to what observed in lymph nodes and peripheral blood mononuclear cells, with the peaks in the early and late stages of infection. A positive correlation was found between viral parameters and TNF-alpha transcription, the strongest relationship was found between the transcription of the cytokine and viral RNA load. These results confirm that invasion of CNS by FIV occurs soon after virus exposure and that during this phase there is an increase of local viral loads with concomitant up-regulation of TNF-alpha expression. During the asymptomatic phase viral replication remains low in spite of the progression of CNS alterations. The dissociation between the viral load and the lesions observed suggests the importance of an indirect mechanism for the progression of these lesions, even if TNF-alpha seems to play a role particularly in the early phase of infection.

Animals↗

Evaluation of the information processing and mood effects of a transdermal nicotine patch.

The purpose of this study was to determine whether a transdermal nicotine patch will produce the same effects on performance and mood as cigarette smoking. The nicotine patch improved attentional processing and produced some improvements in memory. It produced the calming effects of smoking and induced feelings of happiness which were increased with smoking. These effects were obtained 6 h after application of the patch, showing that acute tolerance for these behavioural effects had not developed completely, if at all, after exposure to nicotine, although it is still possible that tolerance might occur with longer exposure.

Administration, Cutaneous↗

Neonatal mouse immunity against group B streptococcal infection by maternal vaccination with recombinant anti-idiotypes.

We investigated whether immunization with recombinant anti-idiotypic antibody fragments mimicking the conformation of the capsular antigen can protect against infection by group B streptococcus, an important neonatal pathogen. Single-chain fragment-variable anti-idiotypes competed with the type III carbohydrate for binding to type-specific antibodies and elicited, in mice, the production of protective immunoglobulins reacting against the type III polysaccharide. Moreover, maternal immunization with soluble or phage-displayed fragments protected neonatal mice against streptococcal infection. These data indicate that recombinant anti-idiotypic antibodies may be useful in developing protein images of relevant carbohydrate epitopes and, ultimately, in preventing infections by encapsulated bacteria.

Agglutination↗

Effect of age upon airway obstruction and reversibility in adult patients with asthma.

OBJECTIVE: In a cross-sectional study we evaluated the effect of aging (separately from that of duration of disease) on airway obstruction and reversibility by comparing two groups of non-smoker patients with asthma. METHODS: We compared two groups of patients: group A, which had 50 subjects (8 men and 42 women) aged 59.7+/-4.6 years (mean +/- SD), and group B, comprised of 51 subjects (19 men and 32 women) who were 35.7+/-7.4 years old. The groups were selected because of comparable baseline degree of obstruction (FEV1 % of predicted, 67.8+/-20.3 in group A; 73.0+/-19.6 in group B, NS) and duration of the disease (14.0+/-11.7 years vs 11.2+/-9.1, NS). Spirometric examination, with a bronchodilator test, was performed and subjects not reaching 85% of predicted were submitted to a 4-week course of inhaled steroids. RESULTS: Although a higher number of subjects from group B responded to the acute bronchodilator test (p < 0.001), the maximum response achievable with treatment (steroid or bronchodilator) (deltaFEV1 expressed as the percent of predicted) was not statistically different between groups (12.0+/-17.5 vs 16.0+/-23.9). The mean FEV1 attainable after treatment (deltaFEV1%PT) was significantly lower in the older group (p = 0.0006). Within groups, the baseline FEV1% did not correlate with age; it was inversely correlated with the duration of the disease (p < 0.03 and p < 0.01, respectively). In both groups deltaFEV1 was inversely related with the baseline FEV1, whereas FEV1%PT was correlated with the duration of the disease, with a slope nearly doubled in group B (p < 0.001). CONCLUSIONS: Both the process of aging and the prolonged exposure to disease effects are important factors in determining the functional characteristics of chronic asthma: In particular, aging is associated not only with a reduced acute responsiveness to bronchodilators, but also with a reduced slope of the duration-FEV1%PT relationship that suggests a slowing of the rate of loss of reversibility of uncertain biological meaning.

Adult↗

Prevention of endotoxin-induced lethality in neonatal mice by interleukin-13.

Interleukin(IL)-13, a cytokine produced by T helper 2 (Th2) cells, is a powerful inhibitor of macrophage functions, including surface expression of CD14 and production of IL-1 and tumor necrosis factor (TNF)-alpha. We tested the effects of recombinant mouse(m)IL-13 in a neonatal mouse model of endotoxin shock; this is a macrophage-dependent condition, which is a model of neonatal sepsis in humans. mIL-13 (0.5 microgram/mouse) dramatically reduced the lethal effects of lipopolysaccharide (LPS) if administered either 24 or 4 h prior to or concomitantly with LPS challenge. This action might be mediated by multiple modulatory activities of IL-13 on LPS-induced cytokine secretion since, relative to control animals, the mice treated with mIL-13 had eight times lower peak blood levels of TNF. The IL-1 beta levels were also decreased, whereas increased levels of IL-6 and IL-10 were observed at several time points after LPS challenge.

Adjuvants, Immunologic↗

Neonatal hypersusceptibility to endotoxin correlates with increased tumor necrosis factor production in mice.

Septic shock is a major cause of mortality in neonates. The hypothesis was tested that neonatal age is associated with altered sensitivity to shock-inducing bacterial products or proinflammatory cytokines (or both). Mice of different ages were inoculated with various doses of lipopolysaccharide (LPS), superantigenic staphylococcal enterotoxin B (SEB), or recombinant tumor necrosis factor-alpha (rTNF-alpha), alone or in combination with the sensitizing agent D-galactosamine. Neonatal mice were markedly more susceptible to LPS-induced lethality but more resistant to SEB than were adults (P < .05). Mice of different ages did not differ, however, in their sensitivity to lethal activities of rTNF-alpha. Neonatal susceptibility to LPS and SEB correlated directly with plasma TNF-alpha but not IFN-gamma levels, which was confirmed by TNF-alpha and IFN-gamma blockade experiments. These data document marked age-related differences in the pathophysiology of septic shock and suggest that IFN-gamma is not an obligatory mediator of either LPS- or SEB-induced lethality in neonates.

Age Factors↗

Interleukin 6 in neonates with early and late onset infection.

OBJECTIVE: To assess the utility of determining interleukin 6 (IL-6) concentrations for diagnosing early (< or = 48 h of life) and late onset infection in a neonatal intensive care setting. METHODS: We measured serum IL-6 values in five groups of neonates on both postnatal Days 1 and 2 (early sampling): Group 1, patients with clinical and microbiologic evidence of early onset infection; Group 2, patients with negative body fluid cultures but strong evidence of infection (clinical septicemia); Group 3, patients without clinical and microbiologic evidence of infection; Group 4, patients in whom infection could be neither confirmed nor excluded; and Group 5, healthy neonates with a normal postnatal course. We also measured IL-6 values in older neonates who during their hospital stay developed systemic infection (late sampling). Three controls matched for duration of hospital stay and birth date were chosen for each patient. RESULTS: On postnatal Day 1 IL-6 values were elevated in all four patient groups compared with those in healthy neonates (P < 0.05 by analysis of variance (ANOVA)). There were no significant differences found among patient groups. On postnatal Day 2 IL-6 concentrations were persistently elevated in Groups 1 and 2 compared with values from those in Group 3, Group 4 and healthy controls (P < 0.01). At this time no significant differences in IL-6 values were found between uninfected symptomatic patients (Group 3), patients with uncertain findings (Group 4) and healthy controls. IL-6 concentrations were significantly higher in patients with late onset infection at presentation than in the patient controls (P < 0.0001) and returned to low values in those who recovered from infection. CONCLUSIONS: There are differences in the serum concentrations of IL-6 that can be helpful in detecting early and late onset infection in preterm and term neonates. During the first 48 h of life serial IL-6 determinations are necessary so as not to overdiagnose infection in a neonatal intensive care setting.

Bacterial Infections↗

Endotoxin-induced lethality in neonatal mice is counteracted by interleukin-10 (IL-10) and exacerbated by anti-IL-10.

The lethal effects occurring in neonatal (<24-h-old) BALB/c mice after challenge with 25 mg of lipopolysaccharide (LPS) per kg of body weight were significantly counteracted by pretreatment with recombinant interleukin-10 (rIL-10; 25 or 50 ng/mouse). Concordantly, blockage of endogenous IL-10 with the SXC1 monoclonal antibody increased LPS-induced mortality. Both IL-10 and SXC1 modulated the release of tumor necrosis factor alpha (TNF-alpha) so that, relative to controls, peak TNF-alpha values after LPS challenge were decreased by rIL-10 and increased by anti-IL-10.

Animals↗

Soluble antigens from group B streptococci induce cytokine production in human blood cultures.

Group B streptococcal antigens stimulated tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 production in human blood cultures in a concentration- and time-dependent fashion. The minimal concentrations of type-specific polysaccharides, lipoteichoic acid, and group-specific polysaccharide required to produce these effects were, respectively, 0.01, 1, and 10 microg/ml. Cell separation experiments indicated that monocytes were the cell type mainly responsible for cytokine production. Time course studies indicated that TNF-alpha was released before the other cytokines. TNF-alpha, however, did not appear to directly induce IL-1beta, as shown by blockade experiments with anti-TNF-alpha antibodies. IL-6 levels were moderately but significantly decreased by anti-TNF-alpha. These data indicate that several products from group B streptococci are able to directly stimulate human monocytes to release TNF-alpha, IL-1beta, and IL-6. These findings may be clinically relevant, since proinflammatory cytokines can mediate pathophysiologic changes during sepsis.

Blood↗

Porins of Pseudomonas aeruginosa induce release of tumor necrosis factor alpha and interleukin-6 by human leukocytes.

The aim of this study was to examine the ability of Pseudomonas aeruginosa components to induce release of cytokines from human leukocytes. Human whole-blood cultures were incubated with several concentrations of purified P. aeruginosa products, including porins, exomucopolysaccharide, lipopolysaccharide, and toxin A. Supernatants were assayed for tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) activities. All of the P. aeruginosa components except toxin A were able to stimulate the release of both cytokines. On a weight basis, porins were as effective as lipopolysaccharide and significantly more effective than exomucopolysaccharide in inducing IL-6 release (P < 0.05). Moreover, porins were more potent than either exomucopolysaccharide or lipopolysaccharide in inducing TNF-alpha release (P < 0.05). Further experiments using isolated leukocytes suggested that monocytes were the cell population predominantly responsible for the production of both cytokines. These data indicate that P. aeruginosa porins are able to induce significant cytokine production. These components may be responsible for the chronically overactive inflammatory response associated with persistent lung infection in cystic fibrosis patients.

B-Lymphocytes↗

Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci.

Cytokines are suspected to play an important role in systemic infections by group B streptococci (GBS), an important cause of neonatal sepsis. This work was undertaken to determine if interleukin 12 (IL-12) is produced in mouse pups infected with GBS and has a role in this sepsis model. IL-12 elevations were measured by both an enzyme-linked immunosorbent assay and a bioassay in plasma samples obtained from 12 to 72 h after GBS challenge. Pretreatment with neutralizing anti-IL-12 antibodies significantly increased lethality and blood CFU (P < 0.05). Conversely, either prophylactically or therapeutically administered recombinant IL-12 (rIL-12) significantly improved survival time and decreased blood CFU. Since these beneficial effects were associated with increased spleen gamma interferon (IFN-gamma) production, we examined whether the latter cytokine mediated the observed rIL-12 effects. Pretreatment with neutralizing anti-IFN-gamma monoclonal antibodies significantly counteracted the beneficial effects of rIL-12 on lethality. Our data indicate that rIL-12 is a possible candidate for treatment of GBS sepsis and that its activities in this model are at least partially mediated by IFN-gamma.

Animals↗

[Non-Hodgkin's lymphoma of the spleen and hepatitis C. Report of a clinical case].

We report a clinical case of a patient affected by splenic non-Hodgkin lymphoma and virus C hepatitis. It seems that this kind of association is original because as far as we know the association between non-Hodgkin lymphoma and HCV did not include non-Hodgkin lymphoma involving the spleen. Indeed, in our patient, there was an increase of CD/57 lymphocytes. In our opinion this could be interesting in the disorders of the immune system associated with lymphoma.

Aged↗