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Biomedical subjects

P Conti

Publications and source records attributed to P Conti.

At least 37 records · Page 2Linked to original sources
PubMed2000

RANTES production and expression is reduced in relapsing-remitting multiple sclerosis patients treated with interferon-beta-1b.

RANTES (regulated upon activation, normal T-cell expressed and secreted), a CC chemokine, appears to play a role in the pathogenesis of relapsing-remitting multiple sclerosis (RR-MS), enhancing the inflammatory response within the nervous system. We have demonstrated that RANTES production is increased in RR-MS compared to controls. Interferon-beta-1b (IFN-beta-1b) treatment reduces RANTES production in sera and peripheral blood adherent mononuclear cell (PBAM) supernatants both in relapse and remission. IFN-beta-1b also reduces RANTES expression in PBAM. Our results suggest that RANTES modulation might represent one of the mechanisms of action of IFN-beta-1b in RR-MS.

Adjuvants, Immunologic↗
PubMed2000

In situ X-ray absorption spectroelectrochemical study of hydroxocobalamin.

An in situ X-ray absorption spectroscopy (XAS) spectroelectrochemical study of aquocobalamin (system B12a-B12r-B12s) has been carried out in aqueous solutions buffered at different pH values. To the best of our knowledge, this is the first structural study of aquocobalamin at room temperature under controlled oxidation conditions. Most of the previous work was in fact performed using frozen samples chemically treated to produce the species. The spectroelectrochemical approach offers several advantages: (1) the reduction products may be studied without poisoning the system with chemical reductive reagents and (2) any possible variation of the oxidation state owing to the electrons produced by the incident beam is avoided as the electrode, under potentiostatic control, acts as a scavenger. The spectroelectrochemical approach, together with more careful data analysis, has led to an improved interpretation of the XAS data. These conditions were not met in previous works where the oxidation state was not controlled and multiple scattering contributions were not taken into account. The general shape of the XAS spectra of the different species is not greatly affected by pH. A signature for the base-off square-planar coordination has been evidenced for the Co(II) compound at basic pH. A new signature for Co(I), indicating square-planar coordination, has been identified on the experimental spectra and simulated in theoretical X-ray absorption near-edge structure (XANES) studies. The flexibility of the electrochemical approach, that permits to unambiguously establish the formal oxidation state, has led to very reliable values for energy shift and peak intensity variations. The experimental XANES and extended X-ray absorption fine structure (EXAFS) spectra with a very good signal-to-noise ratio have been processed using the GNXAS package that takes into account multiple scattering contributions. EXAFS and XANES independent analysis result in the same structural model. The reduction from Co(III) to Co(II) produces the most significant structural changes: the cobalt coordination number decreases from six to five, and the edge position shifts by 2.4 +/- 0.3 eV. In addition, the XANES spectra are strongly modified. The reduction from Co(II) to Co(I) produces mainly electronic effects with no apparent change of the coordination number. A discussion of the limits and potentialities of EXAFS in this type of study has also been included.

Absorptiometry, Photon↗
PubMed2000

Design of new analogues of glutamic acid with a conformationally restricted structure.

Regioisomeric 3-carboxyisoxazolinyl prolines (CIP-A and CIP-B) and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. CIP-A [(+/-)-6] showed a convulsant activity evaluated in vivo on DBA/2 mice, higher than AMPA and similar to kainic acid. The eutomer of CIP-A [CIP-AS, (-)-6], obtained from (S)-3,4-didehydroproline, evidenced common stereochemical requirements with AMPA and kainic acid.

Animals↗
PubMed2000

Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic women exposed to an urban environment.

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.

Adult↗
PubMed2000

Increase in CD45RO+ cells and activated eosinophils in chronic allergic conjunctivitis.

We assessed the infiltration of CD45RO+ cells in conjunctival biopsies of fifteen subjects affected by seasonal allergic conjunctivitis by means of immunohistochemistry. Correlations between infiltration of CD45RO+ cells and serum and mucosal indices of eosinophilic activation were investigated. The study was performed in autumn and all selected patients showed < > also in absence of sensitising pollens. Fifteen healthy subjects were used as controls. The semi-quantitative count of CD45RO+ cells in biopsy specimens demonstrated that positive cells were higher in allergic patients than in controls (p < 0.001) and EG2+ eosinophils were present only in biopsies of allergic patients. Furthermore, a statistically significant positive correlation (r = 0.73; p < 0.001) between CD45RO+ lymphocytes and EG2 positive eosinophils, was observed in the biopsies of allergic patients. Total serum IgE significantly correlated with CD45RO+ cells (r = 0.61; p < 0.02) and EG2+ eosinophils (r = 0.67; p < 0.01) in the conjunctiva. On the other hand serum ECP did not correlate with any histological and immunohistochemical parameters in the conjunctival biopsies. The present study shows that mild symptoms in SCA patients out of pollen season are associated with inflammation of the conjunctiva as shown by an increased number of CD45RO and EG2 positive cells.

Adolescent↗
PubMed2000

Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel challenge in nickel-sensitized women.

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.

Administration, Oral↗
PubMed1999

Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists.

Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortical wedge preparation. CIP-A showed a good affinity for both 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and kainic acid (KAIN) receptors. These results were confirmed in the cortical slice model where CIP-A displayed an EC(50) value very close to that of AMPA. The convulsant properties of all the compounds were evaluated in vivo on DBA/2 mice after icv injection. CIP-A showed a convulsant activity, measured as tonus and clonus seizures, 18-65 times higher than that produced by AMPA. It was also quite active after ip administration, since it induced seizures in mice at doses as low as 3.2 nmol/mouse. On the basis of the above-reported results we prepared and tested the enantiomers of CIP-A and CIP-B, obtained by reacting (S)-3,4-didehydroproline and (R)-3,4-didehydroproline, respectively, with ethoxycarbonylformonitrile oxide. In all the tests the S-form, CIP-AS [(-)-6], emerged as the eutomer evidencing common stereochemical requirements with the reference compounds AMPA and KAIN. Through modeling studies, carried out on CIP-A, AMPA, and KAIN, active conformations for CIP-AS and AMPA at AMPA receptors as well as for CIP-AS and KAIN at KAIN receptors are suggested.

Animals↗
PubMed1999

Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo.

Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. However, the exact role, function, and implication in inflammatory diseases remain to be determined. Here we report that subcutaneous injections (0.2 ml) of a saturated water solution (1:40) of potassium permanganate crystals induces the generation of granuloma tissue at the site of injection in the rat, and reaches its peak of formation after 1 week. The size and weight of the granulomas were increased by i.p. lipopolysaccharide (LPS) (6 microgram/200 microliter) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 300 microgram/200 microliter) treatments in rats, injected 18 hours before sacrifice. Moreover, steady-state levels of MCP-1 mRNA in the granuloma tissue (control), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-treated) whereas in animals treated with Dxs, there was a decrease in (P < 0.05) in formation of mRNA protein. When the granuloma tissues were homogenized the generation of MCP-1 was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in the Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples were further incubated in vitro with LPS (100 ng/ml) overnight. A Strong increase (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calcified tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dxs.

Animals↗
PubMed1999

Expression of lymphocyte subpopulations, cytokine serum levels, and blood and urinary trace elements in asymptomatic atopic men exposed to an urban environment.

The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.

Case-Control Studies↗
PubMed1999

Systemic effects of ingested nickel on the immune system of nickel sensitised women.

This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women (group B) were non-symptomatic, while 7 Ni-sensitised women (group C) showed a flare up of urticaria and/or eczema. Serum and urine Ni were greatly lower before Ni administration than after 4 and 24 hours, without difference among the 3 groups. Before treatment, group B and C showed higher values of blood CD19+ and CD5--CD19+ cells than group A, while group C showed higher serum interleukin (IL) 2 and lower serum IL-5. Four hours after Ni ingestion, group C showed significant increase in serum IL-5. Twenty-four hours after treatment, group A showed a significant reduction in blood CD4+-CD45RO- "virgin" cells and an increase of CD8+ lymphocytes, while group C showed a marked decrease in total blood lymphocytes and CD3+, CD4+-CD45RO-, CD4+-CD45RO+, CD8+, CD19+ and CD5--CD19+ cell subsets. These data may be explained with migration of lymphocytes in tissues with a Th0-like immune response, as shown by the elevated serum IL-2 and the increase of serum IL-5 during the test.

Adolescent↗
PubMed1999

Effect of electromagnetic fields on several CD markers and transcription and expression of CD4.

We carried out flow cytometric analysis for multiparametric evaluation of cell surface markers related to cellular functions. Specifically, we studied the expression of CD4, CD8, CD3, CD16, CD19, HLA-DR, and CD14 macrophage receptors expression and cell cycle progression on cells exposed to ELF-EMF. In addition, we tested the effects of ELF-EMF on CD4 mRNA protein transcription and translation and the cell-cycle progression using an immunofluorescence method. Our data show that same CD surface marker expression are weakly influenced by electromagnetic fields, with no differences between cells exposed or not exposed to ELF-EMFs. However, when the CD4 protein generation was studied, an indication of protein production was found in lymphocytes exposed to ELF-EMF, as evidenced by immunofluorescence, Western blotting and RT-PCR analysis. CD16 and CD14 expression were affected by EMF exposure at all times studied (24, 48, 72 h). The results obtained with cell cycle analysis show that after 48 h of exposure to ELF-EMF, PHA-activated and not activated cells in S phase increase with respect to non-exposed cells. The findings from this study demonstrate that under our defined experimental conditions there is evidence that ELF-EMF has a slight effect on CD4, CD14 and CD16 receptor expression, while the other CD receptors are not affected.

Antigens, CD↗
PubMed1999

Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M.

Two subseries of nonquaternized (5a-10a) and quaternized derivatives (5b-10b) related to oxotremorine and oxotremorine-M were synthesized and tested. The agonist potency at the muscarinic receptor subtypes of the new compounds was estimated in three classical in vitro functional assays: M1 rabbit vas deferens, M2 guinea pig left atrium and M3 guinea pig ileum. In addition, the occurrence of central muscarinic effects was evaluated as tremorigenic activity after intraperitoneal administration in mice. In in vitro tests a nonselective muscarinic activity was exhibited by all the derivatives with potencies values that, in some instances, surpassed those of the reference compounds (i.e. 8b). Functional selectivity was evidenced only for the oxotremorine-like derivative 9a, which behaved as a mixed M3-agonist/M1-antagonist (pD2 = 5.85; pA2 = 4.76, respectively). In in vivo tests non-quaternary compounds were able to evoke central muscarinic effects, with a potency order parallel to that observed in vitro.

Animals↗
PubMed1999

Vitamin B6-deficient diet plus 4-deoxypyridoxine (4-DPD) reduces the inflammatory response induced by T. spiralis in diaphragm, masseter and heart muscle tissue of mice.

Animals fed diets deficient in vitamin B6 develop microcytic anemia, alterations of growth, and other pathologies. 4-deoxypirydoxine is a potent antagonist of vitamin B6 coenzyme which depresses IL-1, TNF and IL-6 and has anti-inflammatory properties. The aim of this study was to show the anti-inflammatory effects of 4-DPD on chronic inflammation caused by the nematode parasite T. spiralis, specifically on the recruitment and the activation of inflammatory cells. Two groups of mice, 6 weeks of age, were used: one was maintained on a vitamin B6-deficient synthetic pellet diet for 15 days before injection of the nematode, and administered an intraperitoneal injection (i.p.) of 4-DPD (250 microg/mouse) for 15 days (the first, 5 days before infection), and the second group was maintained on a normal diet for the total duration of the experiment. These two groups were then injected with 150 larvae (L1-T7 spiralis) per os. Chronic inflammation was caused by infection of treated or untreated mice with T7 spiralis parasite. After 14 days post-infection all mice developed a chronic inflammatory response. Mice fed with a B6-deficient diet showed a significant decrease in the number of cysts found in the diaphragm when compared to mice treated with normal diet. In addition, in all mice treated with vitamin B6-deficient diet plus 4-DPD the average body weight was significantly lower, compared to the mice on normal diet in all weeks examined. Moreover, in sections of the diaphragm, masseter and myocardium muscles, the infiltration of inflammatory cells, such as macrophages, lymphocytes, and eosinophils were more intense in untreated mice compared to those fed a vitamin B6-deficient diet. These results show that BALB/c mice infected with T. spiralis and fed a vitamin B6-deficient diet plus the vitamin B6 antagonist, 4-DPD, prolong the time of invasion of the larvae in the muscle cells, influence the recruitment of inflammatory cells and the intensity of the inflammatory reaction compared to infected untreated mice (control).

Animals↗
PubMed1999

IgG, IgG1 and IgM response in Trichinella spiralis-infected mice treated with 4-deoxypirydoxine or fed a Vitamin B6-deficient diet.

The aim of this study was to investigate the effect of pyridoxine (Vitamin B6) deficiency on the immunological response of BALB/c mice infected with the parasite T. spiralis. Specific anti-parasite IgM and IgG immunoglobulins were detected by ELISA method in the serum of treated animals at different periods for 60 days post infection. Vitamin B6-deficiency was induced in two separate groups of mice by either (1) maintaining the mice on a Vitamin B6-deficient synthetic pellet diet for 40 days before infection, or (2) by daily intraperitoneal injection of 8 x 10(5) M/100 microl of 4-Deoxypyridoxine (4-DPD), a potent antagonist of Vitamin B6 for 20 days prior to infection. These two groups of mice were then injected with 100 larvae (L1-T. spiralis) per os. Parasite burdens in the mice were observed by light microscopy. Cysts were present in the diaphragms of the mice after 60 days post-infection. Parasite specific IgG, as well as IgG1 levels were determined in the sera of infected mice fed a normal diet. These levels were found to be lower in the 4-DPD-treated mice compared to the untreated mice. The inhibition started from the 10th day and continued to the 60th day, and in the 4-DPD-treated group the inhibition initiated after 24 h to 60 days. IgM level also was depressed by 4-DPD, starting from 24 h after injection of the compound. In mice fed Vitamin B6-deficient diets the levels of IgG were lower than in mice fed normal diets. These results show that BALB/c mice infected with T. spiralis and fed either a Vitamin B6-deficient diet or a diet which included the Vitamin B6-antagonist, 4-DPD, both influence the course of IgG, IgG1 and IgM production.

Animals↗
PubMed1999

Impact of extremely low frequency electromagnetic fields on CD4 expression in peripheral blood mononuclear cells.

There is increasing evidence suggesting that extremely low frequency electromagnetic fields (ELF-EMF) may influence several cell functions. Here the effects of ELF-EMF were studied on the expression of CD4+ cell surface receptors of human peripheral blood mononuclear cells (PBMC) using fluorescence-activated cell sorter (FACScan). The expression of CD4+ in ELF-EMF exposed (24, 48 and 72 h) and not exposed PBMC were not statistically significant. In addition, a flow cytometric analysis was determined by using a fluorescent labeled antibody, at 24 and 72 h incubations. The amount of bound antibody was distributed with a slight difference in the ELF-EMF-exposed PBMC compared to the not exposed cells. Moreover, DNA CD4+ expression in PBMC strongly increased in exposed cells, resting and activated with Phytohaemaglutinin (PHA). When polymerase chain reaction was performed on CD4+ mRNA of PBMC an increase of CD4+ mRNA expression was found after the resting cells were exposed to ELF-EMF at 24 h compared to not exposed cells, while at 48 and 72 h no difference was found. In the cell cycle progression analysis, the PBMC exposed to ELF-EMF presented a significant increase of percentage expression of cell cycle progression in the S phase compared to not exposed cells; while in G1 and G2 phases, there were no differences. Our results provide new evidence that ELF-EMF can affect CD4+ expression in PBMC and describe an additional biological activity for ELF-EMF affecting CD4+ transcription and translation protein and the increase of the percentage expression of the cell cycle progression of the S phase.

Blotting, Western↗
PubMed1998

Expression of lymphocyte subpopulations, cytokine serum levels and blood and urine trace elements in nickel sensitised women.

In this study, 20 non-allergic and 20 non-atopic women sensitised only to nickel (Ni) showed similar levels of urine and serum Ni and serum chromium (Cr). On the contrary, serum copper, a marker of inflammation, was significantly higher in the Ni-sensitised group. Sensitised women also had higher values of blood B CD19+, CD5--CD19+ and B and natural killer CD3--CD25+ lymphocytes, but not alterations of some other lymphocyte subsets and serum cytokines. Urine Ni was correlated with "memory" CD4+-CD45RO+ lymphocytes in the non-allergic women and with T CD4+-CD45RO+ and CD3+-CD25+ cells in the atopic women; these subjects also showed a statistically significant correlation of serum Ni with B CD5+-CD19+ lymphocytes and serum IL-13. Moreover, serum Cr of both groups of women was positively or negatively correlated with activated HLA-DR+ cells and/or serum IL-5 and interferon gamma. These results (confirming in part those of a previous study on non-allergic men) suggest that both Ni and Cr are involved in mechanisms regulating the immune response and that allergy to these metals could be considered an alteration of their physiological role.

Adolescent↗