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Biomedical subjects

P Conti

Publications and source records attributed to P Conti.

At least 163 records · Page 9Linked to original sources

GCG Stacks: a friendly interface for the GCG programs.

A 'PLUS' stack which provides a friendly user interface for the GCG suite of programs is presented. The interface takes advantage of the whole set of programming tools available in a graphical and object-oriented environment and its major features include: (i) an efficient management of the on-line help documents, and (ii) a flexible editor for macrocommands. The former facilitates finding specific information in the huge documentation bundled with the GCG suite, and the latter is useful whenever several GCG programs must be run in sequence with automatic piping of the intermediate results.

Database Management Systems↗

Effect of the antirheumatic agent Tenidap on CD3, CD4, and CD8 expression and interleukin-1 and leukotriene B4 secretion in human peripheral blood mononuclear cells.

Thymocytes that express the complete CD3-T-cell receptor (TCR) complex are CD4- and CD8-. The CD4+ T-cell population can be subdivided into at least two quite distinct subsets, TH1 and TH2 cells, based upon cytokine expression. Interleukin-1 (IL-1) appears to be required for optimal proliferation of T cells in response to antigen and it seems that in the absence of IL-1, TH2 clones proliferate less in response to antigen. Tenidap is an antirheumatic agent that has an inhibitory effect on IL-1 production. In these studies, we show that isolated human peripheral blood mononuclear cells (PBMCs) treated in vitro with Tenidap (15 micrograms/mL) for 48-h incubations significantly (p < 0.05) enhanced the present of CD4+ expression compared with untreated cells (control), as determined by cytofluorimetric analysis. Lipopolysaccharide and Bacillus Calmette-Guérin were used as positive controls. When the cells were tested for CD3 or CD8 receptor expression, no differences were found between the untreated PBMCs and the treated (15 micrograms/mL Tenidap) cells. No change was found when cells were incubated for 72 h. Moreover, our data show a strong dose-dependent inhibitory effect of Tenidap (15 micrograms/mL) on IL-1 alpha, IL-1 beta, and leukotriene B4 secretion in PBMCs treated overnight. The increased CD4+ expression by Tenidap in PBMCs may suggest an important role for this new antirheumatic agent in immunity and may hold future therapeutic promise for diseases involving IL-1 and leukotriene B4 as mediators.

Antigens, CD↗

Monocyte chemotactic protein 1 (MCP-1) is a mitogen for cultured rat vascular smooth muscle cells.

The involvement of inflammatory mechanisms in the progression of atherosclerosis has recently been suggested. Monocyte chemotactic protein 1 (MCP-1) is a soluble protein which is implicated in acute and chronic inflammatory processes, including atherosclerosis. We evaluated the effect of human recombinant MCP-1 on the in vitro proliferation of rat vascular smooth muscle cells (VSMCs). Incubation of VSMCs with MCP-1 (50-200 ng/ml) in the presence of 0.5% FCS significantly increased cell proliferation, [3H]-thymidine incorporation and the proliferative S fraction, measured by flow cytometry, compared to control cells. The proliferative effect of MCP-1 was specific, as shown by inhibition with a rabbit polyclonal serum to MCP-1. Moreover, the mitogenic effect of MCP-1 was significantly inhibited by downregulation of protein kinase C (PKC) activity and by incubation with H-7, a protein kinase inhibitor, suggesting the involvement of the PKC system. Verapamil, a Ca2+ channel blocker, also reduced the stimulatory effect of MCP-1 on cell proliferation. This study demonstrates that MCP-1 does not merely have a chemotactic activity, but also a mitogenic effect on cultured rat VSMCs.

Animals↗

Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4).

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G1 phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40 saturated crystal solution of potassium permanganate in mice, was studied. Seven days afterwards, all mice developed a subcutaneous granulomatous tissue indicative of chronic inflammatory response at the site of infection. The intraperitoneal administration of L-mimosine (200 microg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls). In addition, in all mice treated with L-mimosine, there was a strong inhibition of tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the minced granulomas. Interleukin-6 was not detected in the serum of treated and untreated mice. These findings show for the first time, that L-mimosine may have an anti-inflammatory effect on chronic inflammation and an inhibitory effect on tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of minced granulomas.

Animals↗

Conjugated linoleic acid: a functional food?

Scientific interest in conjugated linoleic acid (CLA) started in 1987 when Michael Pariza's team of Wisconsin University observed its inhibitory effects on chemically induced skin tumors in mice. Numerous studies have since examined CLA's role in cancer, immune function, oxidative stress, atherosclerosis, lipid and fatty acids metabolism, bone formation and composition, obesity, and diabetes. Still it's not clear yet either through which mechanisms CLA produces its numerous metabolic effects. We now know that CLA contents in cow milk fat can be enriched through dry fractionation, but this knowledge doesn't allow sufficient certainty to qualify this nutrient, as a functional food, capable of increasing well being and reducing the risk of disease.

Animals↗

T lymphocyte subsets and immunoglobulins in intracranial tumor patients before and after treatment, and based on histological type of tumors.

It has been reported that nervous system and peripheral immune system communicate with each other and the peripheral immune status is depressed in some intracranial tumor (ICT) patients pre operatively. Little is known about the immune status of intracranial tumor patients during the post operative survival period. We thus investigated total T cells (CD 11+), helper/inducer (CD4+) T cells, suppressor/cytotoxic (CD8+) T cells, B cells (CD19+) and serum immunoglobulins in peripheral blood in certain ICT patients before and after treatment, and based on the histological type of the tumors. Post treatment analysis were conducted 30 days after surgical removal of tumor tissue in benign brain tumor patients and 30 days after chemo therapy (CT)/radiotherapy (RT) following surgical removal of tumor tissue in malignant brain tumor patients. Decreased CD11+, CD4+ and increased CD8+ T cell counts were observed in both benign and malignant tumor cases before treatment compared with control subjects. After treatment, CD4+ T cell count increased and CD8+ T cell count decreased than their pre treatment levels. Serum IgA and IgG levels were decreased in both benign and malignant brain tumor patients before treatment than in control subjects. Serum IgM level has been increased in both benign and malignant tumor patients before and after treatment than in control subjects. Anaplastic malignant astrocytoma, medulloblastoma and glioblastoma multiforme patients showed higher IgM level than astrocytoma, meningioma and ependymoma patients. In conclusions, the depressed host cellular immunity in benign and malignant tumor patients before treatment may be due to the changes in CD4+ and CD8+ counts in addition to tumour specific immunosuppressive factors. Treatment procedures such as surgery, CT and RT may play certain role in the post operative depressed immunosuppression in malignant tumor patients. Humoral immune mechanism (CD19+) in the ICT patients was less markedly affected.

Adjuvants, Immunologic↗

A scavenger role for nitric oxide in the aged rat kidney.

Progressive ageing is associated with an increment of biomolecules modified through oxidation as a result of the action of free radicals deriving from reactive oxygen species that attack biomolecules. During ageing many alterations of renal functions have been reported. Renal ageing is associated with a progressive decline of glomerular filtration, renal blood flow and augmented vascular resistance. The kidney is a very important source of inducible nitric oxide synthase (iNOS) in both epithelial and vascular structures. In this study we have investigated mRNA and protein iNOS expression and localization and nitric oxide (NO) production in young and aged rats. An increased expression of iNOS occurs in rat kidney during ageing. In the aged rat, an increase in the values of both iNOS-RNA and iNOS protein was observed through rtPCR and Western blot analysis. The activities of three isoforms of NOS were also seen. In the aged rat kidney the production of NO decreased, due to the reduction of the activities of the three NOS. This suggests that in the aged rat a progressive increase of superoxide anion does not imply an increase in the production of NO which functions as a scavenger molecule, causing oxidative stress with accumulation of reactive oxygen species (ROS).

Actins↗

"In vitro" comparative immune effects of different titanium compounds.

Exposure to Ti compounds is today an occupational and environmental health hazard. Object of this study was to determine "in vitro" effects of different Ti salts on cultured human peripheral blood mononuclear cells (PBMC) proliferation and cytokine release. 10(-4) and 10(-7) M Ti compounds did not modify spontaneous PBMC proliferation. Ti dioxide (a biocompatible material and sunscreen component) did not exert effects on phytoemagglutinin (PHA) stimulated PBMC proliferation and on PHA stimulated IFN-gamma and TNF-alpha release from PBMC. On the other hand, 10(-4) M Ti oxalate (with wide industrial applications) and Ti ascorbate (used mainly in agriculture) inhibited about 70% the PHA stimulate PBMC proliferation; both these Ti compounds at 10(-4) and 10(-7) M concentrations significantly inhibited TNF-alpha release, while only Ti oxalate inhibited that of IFN-gamma. Titanocene (used in chemotherapy) did no exert effects on PBMC proliferation but markedly inhibited IFN-gamma and TNF-alpha release. On the whole, this study demonstrates that Ti dioxide is not immunotoxic; Ti oxalate shows marked immunotoxicity; titanocene exerts selective toxicity on cytokine release but not on PBMC proliferation, while Ti ascorbate affects TNF-alpha release from PBMC but not iFN-gamma release. In conclusion, the data show that immunotoxicity fo Ti depends on speciation.

Adult↗

Inhibition of MCP-1 and MIP-2 chemokines in murine trichinellosis: effect of the anti-inflammatory compound L-mimosine.

Mimosine is a plant amino-acid which has been reported to block DNA replication in mammalian cells and to arrest cell reversibly towards the end of the G1 phase or at the beginning of the S phase. In this study, 42 mice were infected with T. spiralis a nematode parasite, and treated with the anti-inflammatory compound L-mimosine, to determine if any alteration in the chronic inflammatory state occurred, by investigating the hosts immunological response. MCP-1, a C-C chemokine and MIP-2, a C-X-C chemokine were tested and calculated in the sera of infected animals, after 1, 10, 20, 30, 40, 50 and 60 days post infection, by ELISA method. The diaphragm and the masseters of the infected mice, were tested for inflammatory response. Here we found, that MCP-1 was partially inhibited by L-mimosine, while MIP-2 was totally inhibited. Moreover in sections of the diaphragm and masseters, the infiltration of inflammatory cells, such as macrophages, lymphocytes and eosinophils were more intense in untreated animals compared to those treated with L-mimosine. These findings show, that L-mimosine may have an inhibitory effect on MCP-1 and MIP-2 serum levels in Trichinellosis and may influence the recruitment of inflammatory cells and the intensity of the inflammatory reaction in this parasitic disease.

Animals↗

Aluminum impairs rat neural cell mitochondria in vitro.

Exposure to aluminum has been reported to lead to neurotoxicity. Mitochondria are important organelles involved in maintaining cell function. This study investigates the effect of aluminum on mitochondria in rat neural cells. The ultrastructure of mitochondria was observed, and the cell death rate (CDR), reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and 3-[4,5demethyl-2-thiazalyl]-2,-5diphenyl-2H-tetrazolium bromide (MTT) were measured to investigate the effect of aluminum on the mitochondrial structure and its function in neural cells. Results observed from the mitochondrial ultrastructure show that aluminum may impair the mitochondrial membrane and cristae. Increased CDR, enhanced ROS, decreased MMP, and decreased enzyme activity in mitochondria were observed in the Al-exposed neurons (100 500 microM). The present study demonstrates that alteration in the mitochondrial structure and function plays an important role in neurotoxic mechanisms induced by aluminum.

Aluminum↗

Chemokines as markers for parasite-induced inflammation and tumors.

Chemokines are a group of small secreted proteins (8-10 kDa) produced and released by a wide variety of cell types. They were originally described as mediators of leukocyte recruitment, which is essential in acute and chronic inflammation. They also play a critical role in many pathophysiological processes such as allergic responses, infections and autoimmune diseases, tumor growth and hematopoietic development. This review introduces the three supergene families of chemokines (CXC, CC and C) with emphasis on their important role in different states in humans and in animal models with parasitic diseases. The concentration of transcription and translation of the cytokines and chemokines in the parasitic diseases may be an important marker for evaluation of the inflammatory state.

Animals↗

Rat basophilic leukemia cells (RBL-2H3) generate prostaglandin D2 (PGD2) after regulated upon activation, normal T-cell expressed and secreted (RANTES) activation.

Increasing evidence indicates that local neurogenic inflammation, possibly in response to different stimuli, may be involved in sensory nerve sensitization, migraine generation and some other precipitating events leading to neuronal dysfunction in the brain. In addition, mast cells generate eicosanoids that are linked to asthma and other inflammatory diseases. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a small protein and a prototype member of the CC chemokine-beta subfamily with chemoattractant and inflammatory properties. In this study we used the RBL-2H3 cell line to determine whether or not these cells generate prostaglandin D2 (PGD2) after treatment with RANTES. After 4 hours of incubation, RBL-2H3 cells cultured with RANTES at 20 ng/mL released large amounts of PGD2 in a dose-response manner compared to control. Moreover, RBL-treated RANTES generated a large quantity of histamine. Our study confirms once again the proinflammatory action of RANTES, in this case acting on the stimulation of the arachidonic acid cascade product PGD2.

Animals↗