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Biomedical subjects

C De Simone

Publications and source records attributed to C De Simone.

At least 91 records · Page 5Linked to original sources
PubMed1995

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact: a possible role for membrane-associated interleukin-6 and interleukin-8.

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.

Adult↗
PubMed1994

Activity of terbinafine against Pneumocystis carinii in vitro and its efficacy in the treatment of experimental pneumonia.

The antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post inoculation. With respect to trimethoprim-sulphamethoxazole and pentamidine isethionate P. carinii organisms decreased at the same time interval but cyst form elimination was less apparent than with terbinafine. The results of the in-vitro culture were consistent with the in-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats (group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among terbinafine treated rats (group 1), P. carinii pneumonia was present in one rat (3.3%), while no P. carinii infection occurred in the pentamidine isethionate and in trimethoprim-sulphamethoxazole treatment rat groups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P. carinii pneumonia.

Animals↗
PubMed1994

Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine.

OBJECTIVE: Reduced levels of serum carnitines (3-hydroxy-4-N-trimethyl-ammonio-butanoate) are found in most patients treated with zidovudine. However, since serum carnitines do not strictly reflect cellular concentrations we examined whether a carnitine depletion could be found in peripheral blood mononuclear cells (PBMC) from AIDS patients with normal serum carnitine levels. In addition, we explored whether it was possible to relate the host's immunoreactivity to the content of carnitine in PBMC and whether carnitine levels can be corrected by oral supplementation of L-carnitine. DESIGN: Immunopharmacologic study. METHODS: Twenty male patients with advanced AIDS (Centers for Disease Control and Prevention stage IVCI) and normal serum levels of carnitines were enrolled. Patients were randomly assigned to receive either L-carnitine (6 g/day) or placebo for 2 weeks. At baseline and at the end of the trial, we measured carnitines in both sera and PBMC, serum triglycerides, CD4 cell counts, and the frequency of cells entering the S and G2-M phases of cell cycle following mitogen stimulation. RESULTS: Concentrations of total carnitine in PBMC from AIDS patients was lower than in healthy controls. A significant trend towards the restoration of appropriate intracellular carnitine levels was found in patients treated with high-dose L-carnitine and was associated with an increased frequency of S and G2-M cells following mitogen stimulation. Furthermore, at the end of the trial we found a strong reduction in serum triglycerides in the L-carnitine group compared with baseline levels. CONCLUSIONS: Our data indicate that carnitine deficiency occurs in PBMC from patients with advanced AIDS, despite normal serum concentrations. The increase in cellular carnitine content strongly improved lymphocyte proliferative responsiveness to mitogens. Because carnitine status is an important contributing factor to immune function in patients with advanced AIDS, we therefore believe that L-carnitine supplementation could have a role as a complementary therapy for HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Increased polymorphonuclear leukocyte Fc gamma-dependent chemiluminescence in active psoriasis is not related to FcRIII (CD16) receptor expression.

The role of the two main serum opsonins (IgG and C3b) in the induction of polymorphonuclear leukocyte chemiluminescence was studied in a group of psoriatic patients. Chemiluminescence was stimulated with zymosan opsonized by fresh plasma (IgG- and C3b-dependent chemiluminescence) or by complement-depleted plasma (IgG-dependent chemiluminescence). While C3b-dependent chemiluminescence was similar in patients with chronic or active forms of psoriasis, IgG-dependent chemiluminescence was significantly increased in patients with active disease. However, FcR-III expression, evaluated by means of flow cytofluorimetry, was similar in the different groups of patients studied. The discrepancy between Fc-receptor (CD16) expression and IgG-dependent chemiluminescence is, therefore, indicative of modifications that occur in psoriatic neutrophils that do not involve FcIII-receptor expression.

Adult↗
PubMed1993

High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients.

Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Supplementation of male inhibitory material to lipid A activated human mononuclear cell supernatants contributes to the suppression of polymorphonuclear cell phagocytosis.

Human normal peripheral blood mononuclear cells were stimulated with lipid A (LA), the biologically active moiety of bacterial lipopolysaccharides. LA-activated supernatants were able to suppress polymorphonuclear cell (PMN) phagocytosis of Candida albicans. This inhibitory activity was enhanced by the supplementation of male inhibitory material (MIM) to active supernatants. The addition of a recombinant human anti-interleukin-1 beta monoclonal antibody to activated supernatants in the absence or presence of MIM diminished or abrogated, respectively, the suppressive effect on PMN function. The mechanisms and the significance of MIM-mediated inhibition of phagocytosis under these circumstances are discussed.

Adult↗
PubMed1992

Importance of the type of soil for the induction of micronuclei and the growth of primary roots of Vicia faba treated with the herbicides atrazine, glyphosate and maleic hydrazide.

Research was carried out on the genotoxic effects (induction of micronucleated cells in primary root tips) and toxic effects (reduction in primary root growth) in young plants of Vicia faba grown in soils with different organic matter contents and treated with the herbicides atrazine, glyphosate and maleic hydrazide. The data obtained show that the genotoxic effects are noticeably influenced by the interactions between the herbicide and the type of soil in which the Vicia faba have grown. While maleic hydrazide proved to be highly clastogenic for young plants grown in both soils, atrazine was genotoxic only in young plants grown in soil poor in organic matter. Glyphosate did not induce micronuclei under either soil condition, but induced a significant toxic effect.

Atrazine↗
PubMed1992

AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin.

In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin.

AIDS-Related Opportunistic Infections↗
PubMed1992

L-carnitine deficiency in AIDS patients.

OBJECTIVE: To evaluate carnitine (3-hydroxy-4-N-trimethyl-ammoniobutanoate) deficiency in AIDS patients by measuring serum total, free and short-chain carnitine concentrations. DESIGN: We conducted an open study. SETTING: All patients were seen at the Infectious Diseases Clinic, Università 'La Sapienza', Rome, Italy. PATIENTS, PARTICIPANTS: Twenty-nine AIDS patients, aged 27-41 years, with a previous history of drug use; and 14 healthy age- and sex-matched controls were studied. INTERVENTIONS: Study subjects were administered 500-800 mg zidovudine daily for 2 to 28 months (8 +/- 6 months). MAIN OUTCOME MEASURES: Carnitine deficiency was suspected in study participants prior to data collection because of previously reported cardiac symptoms, muscle weakness, hypometabolism and/or cachexia. RESULTS: A marked decrease in total and free carnitine was observed in 21 (72%) subjects. Nine of these patients also had low levels of short-chain carnitine. CONCLUSIONS: AIDS patients may become carnitine-depleted and therefore at risk for alterations in fatty-acid oxidation and energy supply.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact. A possible role for membrane-associated cytokines.

Previous findings have shown that lipopolysaccharide (LPS)-activated human monocytes express cytokines (CKs) on their membrane. Furthermore, those associated to membrane products such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been demonstrated to exert many biological activities. In this paper, evidence is provided that human polymorphonuclear cells (PMN) exhibited an increased phagocytic capacity following incubation with either lipid A (LA)-activated autologous monocytes or supernatants recovered from LA-stimulated mononuclear cell cultures. In order to investigate the possible role of monocyte membrane-associated TNF-alpha, IL-1 alpha and IL-1 beta in the modulation of PMN activity, in a separate series of experiments LA-activated monocytes or LA-activated supernatants were pretreated with anti-recombinant human (Rhu) TNF alpha, anti-Rhu IL-1 alpha and anti-Rhu IL-1 beta monoclonal antibodies (MoAbs), respectively. Such an approach gave rise to an abrogation of monocyte-mediated triggering effect on PMN functional capacity. Taken together, these data suggest that activated monocytes can upregulate PMN phagocytosis by a cell-to-cell contact mechanism, likely related to membrane-associated CKs.

Antibodies, Monoclonal↗
PubMed1992

Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes.

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.

Aged↗
PubMed1992

Oral polyvalent vaccine (Buccalin Berna) administration activates selected T-cell subsets and regulates the expression of polymorphonuclear leukocyte membrane molecules.

Acute respiratory tract infections (ARIS) still represent a major clinical problem during influenza outbreaks. The virus-induced impairment of the immune system favors the entry of opportunistic microorganisms into respiratory tract mucosa. A useful strategy to reduce ARIS is to provide at risk subjects an orally administrable polyvalent vaccine (OPV) comprised of bacteria strains recognised as the major ones responsible for ARIS. For the present study, the main circulating leukocyte populations of a group of healthy subjects receiving OPV were monitored as a marker of immune response. Subjects were investigated immediately before taking OPV (day 0) and 10,20, and 30 days later. Data show that T lymphocytes were induced to enhance the expression of class II MHC molecules, whilst a consistent number of CD4+ lymphocytes lost L-selectin, both phenomena indicating an activation status. OPV administration also modulated important molecules on the membrane of polymorphonuclear leukocytes, namely CD11b and CD16, strongly suggesting an activation of these cells and an enhancement of their defensive capacities. Finally, OPV was found to be able to increase the titer of serum antibodies specific for bacteria strains contained in the vaccine preparation in a portion of individuals. We conclude that OPV is able to consistently influence important immune functions and suggest that this property may be of relevance in preventing ARIS. Also, the present data may help to further our understanding of the mechanisms of OPV activity.

Administration, Oral↗