Biomedical subjects

L Paulesu

Publications and source records attributed to L Paulesu.

At least 37 records · Page 2Linked to original sources

PubMed1993

Production of tumor necrosis factor alpha by rat alveolar macrophages collected after acute cigarette smoking.

In this study we evaluated the effect of cigarette smoke on the activation of alveolar macrophages of the rat lungs exposed to an episode of acute passive cigarette smoking. Our experiments were carried out in rats that, after undergoing smoking (3 cigarettes within 1 h) showed a COHb increase of about 16%. The evaluation of the kinetics of alveolar and peritoneal macrophages, indicated that the number of alveolar macrophages in the bronchoalveolar lavage fluids significantly increased 8 h after the smoking session, whereas the number of peritoneal macrophages remained practically constant. Alveolar macrophages collected 0.8 and 24 h after smoking and incubated for 24 h at 37 degrees C in an atmosphere of 5% CO2 in air spontaneously released 5 +/- 1, 48 +/- 14 and 15 +/- 9 units of TNF-alpha per 10(6) cells, respectively. Moreover, neither alveolar macrophages collected from smokers, nor those collected from controls, released IFN, and both cytokines were also absent either in bronchoalveolar lavage and peritoneal lavage fluids or in plasma. Alveolar macrophages collected from controls rats, when challenged with lipopolysaccharide (LPS), released more TNF than those collected from smoke exposed rats. Thus, it seemed that macrophages of experimental animals were activated but at the same time were somewhat depressed and responded less well to LPS.

Animals↗

PubMed1993

The lymphatic route. IX. Distribution of recombinant interferon-alpha 2 administered subcutaneously with oedematogenic drugs.

We have evaluated whether the addition of either bradykinin or histamine favours the lymphatic absorption of human recombinant interferon-alpha 2 (IFN-alpha 2) administered by the subcutaneous route. Subcutaneous administration of IFN-alpha 2 with bradykinin enhances IFN absorption via both capillaries and lymphatics, so that either the plasma or lymph areas under the concentration curves (AUC) increase significantly up to 1751 +/- 483 and 1319 +/- 608 IU/ml/min respectively as compared to the respective AUC values (613 +/- 208 and 483 +/- 213 IU/ml/min) obtained after IFN injection in normal saline. Since the lymph AUC/plasma AUC ratios remain unaltered, there is no preferential lymphatic absorption of IFN-alpha 2 after bradykinin administration. Dual-label experiments, 125I-IFN-alpha 2 in saline and 131I-IFN-alpha in saline containing 200 micrograms histamine were injected subcutaneously into the left and into the right shank of the same animal, gave similar results. The kinetics of 125I and 131I acid-soluble radioactivity confirm that histamine favours both plasmatic and lymphatic absorption.

Animals↗

PubMed1993

Studies on the biological effects of ozone: 3. An attempt to define conditions for optimal induction of cytokines.

Ozonization of blood, normally carried out with citrated blood, may be fine for the autohemotherapy of ischemic diseases but it may be at a loss when employed in viral diseases or in immunodeficiencies. We have shown that heparin, used as an anticoagulant, with the addition of 5 mM CaCl2 favors production of cytokines by leukocytes with only a modest increase in hemolysis. High plasmatic levels of glucose, glutathione, and ascorbic acid decrease cytokine's yield because these compounds act as antioxidants and quench the inducing activity of ozone. Autohemotherapy with heparinized and Ca(2+)-supplemented blood has not revealed any side effects in volunteers.

Blood↗

PubMed1993

Presence of interferon-gamma and interleukin-6 in colostrum of normal women.

Colostrum and blood samples were obtained on postpartum day 2 and 3 from 17 lactating, healthy women. After delipidation and molecular sieving fractionation of colostrum, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) could be readily measured by using a sensitive immunoassay. Antiviral activity could be also measured in some colostrum samples suggesting that interferon was biologically active. On the contrary, corresponding plasma samples showed negligible activity. These results expand previous data showing the presence of IL-1, tumor necrosis factor (TNF-alpha), and IL-6 in normal colostrum and are in line with the concept of a basal cytokine production in physiological conditions. All of these cytokines probably act on the oropharyngeal and gut-associated lymphoid tissue of the newborn and favor the development and maturation of the immune system.

Adult↗

PubMed1992

Effect of tuftsin and its retro-inverso analogue on the release of interferon (IFN-gamma) and tumor necrosis factor (TNF-alpha) by human leucocytes.

The aim of this work was to demonstrate whether natural tuftsin or a retro-inverso (r.i.) analogue may induce interferon (IFN) and tumor necrosis factor (TNF) in peripheral-blood-mononuclear-cells (PBMC). For this purpose tuftsin or its analogue were added at different molar concentrations to PBMC and the supernatants were tested for IFN and TNF activity. Both cytokines were released after 12 hours incubation with r.i. tuftsin at an optimum concentration of 10(-10) M. Under the same conditions no activity was observed in the presence of natural tuftsin. In comparison to natural tuftsin the stimulatory activity of this tuftsin analogue is likely to be due to its high stability.

Adult↗

PubMed1992

Human beta-interferon incubated with muscle homogenate is protected by albumin but not by proteinase inhibitors.

The scarce bioavailability of beta-interferon (IFN-beta) after intramuscular administration is probably due either to the binding of IFN-beta to interstitial matrix, or to lymphatic absorption and/or to local breakdown by lysosomal proteinases from muscle. In this work, we first showed that after intramuscular injection, the apparent bioavailability of natural human IFN-beta is about 10% of that of recombinant IFN-alpha 2 and then we evaluated the effects of proteinase inhibitors and albumin on IFN-beta incubated at 37 degrees C with muscle homogenate. IFN biological activity decreased spontaneously by about 20% after incubation for 6 hr at 37 degrees C in Hanks' solution, but it was almost completely lost after incubation with muscle homogenate. Proteinase inhibitors (alpha 1-antitrypsin, alpha 2-macroglobulin, aprotinin, soybean trypsin inhibitor, leupeptin, EP-459, and EP-475) failed to block the inactivation of IFN-beta by muscle proteinases, whereas albumin exerted a partial but consistent protection.

Albumins↗

PubMed1991

Interferon induction in rabbits after intraduodenal administration of a phosphorylated glucomannan-protein fraction of the cell wall of Candida albicans.

The aim of this work was to demonstrate whether a glucomannan protein fraction (GMP) of Candida albicans cell wall could induce interferon after intraduodenal administration in normal rabbits and rabbits immunized against C. albicans. For this purpose we collected simultaneously plasma and abdominal lymph for 10 h after the administration of the inducer. We observed a peak of antiviral activity in the lymph 4 h after intraduodenal administration of 20 mg GMP dissolved in saline to 6 normal rabbits. Immunized rabbits (anti-GMP titres greater than 1024) responded earlier (peak after 2 h) and more intensely; analysis of the values of the areas under the curve indicated that the IFN response in the lymph of immunized rabbits was significantly higher (P less than 0.0025) than in normal rabbits. Antiviral activity was absent in plasma in all cases. Preliminary characterization of the IFN activity has shown it to be trypsin-sensitive, acid and heat stable, and species-specific.

Animals↗

PubMed1991

Studies on the biological effects of ozone: 2. Induction of tumor necrosis factor (TNF-alpha) on human leucocytes.

The effect of ozone as a probable inducer of tumor necrosis factor (TNF-alpha) has been investigated on human blood and on Ficoll-purified blood mononuclear cells (PBMC). Samples were exposed at different ozone concentrations ranging from 2.2 to 108 micrograms/ml and incubated at 37 degrees C in an 95% air-5% CO2 atmosphere. At predetermined times, all cell supernatants were tested for TNF activity and some PBMC cultures were examined for DNA synthesis. We have shown that ozone concentration is critical in terms of TNF production and of cell mitogenesis and that, owing to the presence of erythrocytes, higher ozone concentrations are required to be effective in blood than in PBMC. Because ozonization of blood is a procedure followed in several European countries for the treatment of viral diseases and tumors, the release of factors with antiviral and immunomodulatory activities by leukocytes may explain the mechanism of action of ozone and of autohemotherapy.

Enzyme-Linked Immunosorbent Assay↗

PubMed1991

Immunohistochemical localization of IL-1 alpha and IL-1 beta in normal human placenta.

Many reports show that interleukin 1 (IL-1) is produced by mouse and human placenta but the cell type that is responsible for this production has yet to be identified. For this reason we attempted to localize IL-1 alpha and IL-1 beta directly on formalin-fixed paraffin-embedded normal human placentae at different stages of pregnancy using immunohistochemical techniques and specific antibodies. The results obtained show that both IL-1 forms are localized to villous syncytiotrophoblast and to extravillous trophoblast, while villous cytotrophoblast and cytotrophoblast columns are unreactive. A gradual decrease of reactivity was observed with increasing gestation age for both IL-1 forms, but the staining for IL-1 beta was in all sections higher than for IL-1 alpha. Although the physiological role of IL-1 in pregnancy has yet to be established, the presence of this cytokine in the cells facing maternal blood and tissues suggests a possible involvement in the immunoregulation of fetal acceptance.

Female↗

PubMed1988

The lymphatic route. V. Distribution of human natural interferon-beta in rabbit plasma and lymph.

Human natural interferon-beta (HuIFN-beta) was administered through different routes (intravenous [i.v.], intramuscular [i.m.], and subcutaneous [s.c.]) and its distribution in lymph and plasma was evaluated. After i.v. (bolus) administration the lymph/plasma ratio was about 0.35 but it significantly increased (11-fold) after i.m. administration. Addition of human albumin (ALB) to the IFN solution did not favor IFN absorption through the lymphatics. On the other hand, addition of ALB improved IFN absorption through the lymphatics after s.c. administration. These results are interesting because they clarify why IFN-beta can exert immunomodulatory activities in spite of very low plasma levels.

Animals↗

PubMed1988

The physiological interferon response. IX. Interferon activity in rabbit lymph after intraduodenal administration of alimentary lectins.

The physiological interferon (IFN) response involves the production of little amounts of IFN in localized lymphoid microenvironments upon induction of exogenous and endogenous inducers. The aim of this work was to demonstrate whether dietary antigens and/or alimentary lectins could induce IFN in vivo after intraduodenal administration in rabbits. For this purpose we have collected simultaneously the abdominal lymph and plasma during the experiments for about 12 hours. The results show that while both onion' (Allium cepa) and cucumber' (Cucumis sativum) homogenates are ineffective, the hydrolysate of the latter induces a marked increase of IFN in the lymph suggesting that preliminary digestion (and probably gastric digestion) is crucial for the activation of IFN inducers. The maximum IFN activity occurs 7 hours after the administration and there is no concomitant activity in the plasma. Addition of bile salts to either the homogenates or the hydrolysates in unable to modify the pattern of the response. Preliminary characterization of the IFN activity has shown it to be trypsin-sensitive acid- and heat-stable and species-specific.

Animals↗

PubMed1988

The lymphatic route. VI. Distribution of recombinant interferon-alpha 2 in rabbit and pig plasma and lymph.

Human recombinant (R) interferon-alpha 2 (either cold or labeled with 125I or 131I) has been administered through different routes [intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.)] and its distribution in lymph and plasma has been evaluated in rabbits and pigs. After i.v. (bolus) administration, the lymph/plasma ratio was about 1. After s.c. and i.m. administration, the ratio varied from an average of 0.8 up to 2, respectively, indicating that R interferon-alpha 2 is preferentially absorbed via lymphatics when injected into the shank muscles. Another novel result is that the ratio is markedly increased after s.c. administration of interferon-alpha 2 with a solution containing 12.5% human albumin. In this case, albumin acts as an interstitial fluid expander, thereby increasing the fluid pressure and favoring lymphatic absorption. Similar results were obtained using either cold or labeled interferons in rabbits; moreover, the effect of albumin was confirmed in the pig by simultaneously injecting 131I-interferon (in saline) and 125I-interferon (in albumin solution) in the left and right subcutis of the shanks, respectively. All of these data suggest that the indirect lymphatic route is a feasible proposition, and that by modifying the absorption, the distribution and fate of interferon may improve the therapeutic index of biological response modifiers.

Animals↗

PubMed1987

DNA synthesis and interferon release by human peripheral lymphocytes exposed to high potassium medium.

Lymphocytes have their membrane potential changed during transition from the resting to the active state. On these grounds, we investigated the response of human peripheral lymphocytes to a depolarizing high-potassium (102.7 mM) medium, by assaying cellular incorporation of labeled thymidine and interferon (IFN) release in the culture medium. The greatest effect is evident 3-4 days after preincubation for 120 min in high K+ medium. A temporal correlation has been observed between rate of DNA synthesis and IFN production. The IFN activity is shown to be gamma-type.

Cells, Cultured↗

PubMed1986

Presence of interferon in venous blood draining from gut-associated lymphoid tissue.

The question has been examined of whether interferon (IFN), produced in the microenvironment of the gut-associated lymphoid tissue (GALT) during the physiological response, is consumed locally, or whether some spills over and is drained into the general circulation. Plasma IFN levels were measured in venous blood draining from abdominal organs that are normally in contact with exogenous and endogenous interferon inducers. The results obtained from three rodent species indicate the presence of a venous-arterial and GALT venous-peripheral venous gradient, suggesting that at least some of the IFN produced in the GALT and spleen is absorbed via blood capillaries and detectable in the regional vessels. Owing to the rapid turnover of IFN, arterial or peripheral venous blood showed a basal level. The antiviral activity (AA) in rat and mouse blood appears to be attributable to IFN-gamma.

Animals↗

PubMed1985

Interferon production in BCG-sensitized rabbits challenged with PPD.

Intravenous administration of PPD into BCG-primed rabbits results in the release of IFN into the circulation. Peak interferon titres occur in plasma 1 h after PPD injection, rapidly decline during the following 3 h and depend on the dose of tuberculin administered. Bilateral nephrectomy of BCG-primed rabbits challenged with PPD affects remarkably the disappearance of IFN from the circulation. Characterization of the BCG-PPD-induced IFN shows that it is heat-labile, is almost completely inactivated after dialysis at pH 2 and displays a remarkable cross-species activity, particularly on human cell lines.

Animals↗

PubMed1985

Pharmacokinetics of human lymphoblastoid interferon in rabbits.

By intravenous (bolus) administration of large amounts (29 Mega Units) of lymphoblastoid interferon into rabbits, it has been possible to detect circulating antiviral activity (0.02% of the dose) up to 18 hr post-injection and to determine for the first time the pharmacokinetic parameters. The slow component (elimination phase) has a half-life of 235 +/- 9 min. The total apparent volume of distribution is 2,564 +/- 1,497 ml which is far larger than the combined plasma-extracellular volumes. This suggests a IFN dilution due to its extensive binding to cell receptors. The clearance of 7.3 +/- 4.1 ml/min is an index of the rate of renal and cellular (internalization of the receptor-ligand complex) catabolism of IFN. Pharmacokinetic parameters are useful for devising an administration schedule of IFN as an antiproliferative agent but are not predictive of an immunological response if IFN is used as an immuno-adjuvant.

Animals↗

PubMed1985

Catabolic sites of human interferon-gamma.

Recombinant human interferon-gamma (HuIFN-gamma) injected into rabbits disappeared from the circulation more rapidly than natural IFN-gamma. The latter displayed an initial decay curve more rapid than that for natural HuIFN-alpha although 4 h after injection plasma levels were similar. This result suggests that IFN-gamma has pharmacokinetic properties different to those of IFN-alpha which may be explained by considerable and simultaneous hepatic and renal catabolism. Surprisingly, the hepatic uptake of recombinant (unglycosylated) IFN-gamma was more marked than uptake of natural IFN-gamma. Moreover, both IFN-gamma preparations were cleared by the isolated and perfused kidney and once again the recombinant IFN disappeared more rapidly. This result does not conform with the suggestion that IFN-gamma exists as a tetramer which would not be filtered by the glomerulus, but is consistent with the pharmacokinetic behaviour shown in vivo.

Animals↗

PubMed1985

Effect of exercise on plasma interferon levels.

The effect of exercise on plasma interferon activity was studied on eight male subjects before and after exercise on a bicycle ergometer for 1 h at 70% of their maximal O2 consumption (VO2 max). Acid-labile interferon, alpha-type according to immunological characterization, rose significantly from a preexercise value of 3 +/- 1 to 7 +/- 2 IU/ml postexercise. Negligible changes were recorded for plasma protein, lipid, and glucose concentrations, whereas blood lactate slightly increased only at the end of exercise. According to hematocrit and plasma protein values before and after exercise, hemoconcentration did not occur. These data provide evidence that plasma interferon activity increased following a bout of submaximal exercise.

Adult↗