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Biomedical subjects

V Bocci

Publications and source records attributed to V Bocci.

At least 55 records · Page 3Linked 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

Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis.

In the last 3 decades major autohemotherapy after exposure to ozone has been used in Europe in uncontrolled trials carried out in patients with many illnesses, particularly chronic viral diseases and neoplasms. It appears that the treatment may activate the host's immune system by inducing the production of immunoactive cytokines and it may now be possible to rationalize the procedure, improve the regimen and assess the outcome. It is apparent, however, that such a therapeutic approach, in order to be acceptable, requires an investigative effort of biologists and clinicians. Once this is done, owing to the large range of medical applications and the simplicity of the procedure, autohemotherapy could become very valuable particularly in underdeveloped countries.

Blood Transfusion, Autologous↗
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↗
PubMed1992

Physicochemical and biologic properties of interferons and their potential uses in drug delivery systems.

Interferons (IFNs) are a complex group of proteins and glycoproteins able to express antiviral, immunomodulatory, and differentiation activities. In physiological conditions, they are produced upon induction, in basal amounts, and in restricted microenvironments where they act in a paracrine fashion, hardly reaching the circulation and not affecting parenchymal cells. In some acute infections, production of IFN is diffused and, therefore, IFN levels become detectable in plasma, and side effects, such as the typical flu-like syndrome, ensue. A similar situation occurs during pharmacological therapy, particularly when IFN is administered through conventional routes (IV, IM, and SC). We have finally realized that IFNs are normally not circulatory proteins, and because they are unselective during therapeutic intervention, toxicity can overcome beneficial effects. For this reason, there is a pressing need to optimize treatment, dosages, and schedules for improving the therapeutic index. A further important issue is the definition of routes of IFN administration able to achieve the maximal activity where needed, and in fact, when IFNs are used as cytostatic drugs, regional therapy improves the treatment. However, when IFNs are used as immunomodulatory agents, other strategies must be sought, and the interaction of IFN with epithelial membranes and mucosal associated lymphoid tissue becomes important. Hence, delivery via oropharyngeal, intestinal, rectal, bronchioalveolar, and lymphatic routes appears useful probably because they simulate the physiological distribution and action of IFNs.

Drug Administration Routes↗
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

Interleukins. Clinical pharmacokinetics and practical implications.

Interleukins and tumour necrosis factor (TNF) are a complex group of proteins and glycoproteins able to exert pleiotropic effects with respect to a number of different target cells. In physiological conditions, they are induced and released in basal amounts only in restricted microenvironments where they have paracrine activity. Any small amounts reaching the circulation do not disturb homoeostasis. During therapy, particularly when these cytokines are administered via conventional routes, it has become apparent that their presence in nonphysiological plasma concentrations and their unselective action cause toxic effects with small benefits. The pharmacokinetics of interleukins-1, -2, -3 and -6 and TNF have been evaluated, and their disappearance from plasma after intravenous administration is very rapid (i.e. the distribution half-life is measured in minutes; the elimination half-life is several hours). The efficiency of catabolic pathways such as renal filtration and/or liver uptake is interpreted as a salutary mechanism for extracting proteins that should not be in the circulation. However, because these cytokines are very potent immunomodulatory agents there is a need to improve their therapeutic index, and to this end a number of possible formulations and routes of administration are now available and may eventually be of practical use.

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↗
PubMed1990

Metabolic behavior and distribution of the synthetic nonapeptide fragment 163-171 of human IL-1 beta.

The pharmacokinetic parameters and distribution of the adjuvant synthetic nonapeptide VQGEESNDK, corresponding to the fragment in position 163-171 in human IL-1, were analyzed after administration to rabbit through different routes. The radiolabeled peptide did not bind to plasma proteins and, when inoculated i.v., it disappeared very rapidly from the circulation, with a t1/2 alpha of 1 min and a t 1/2 beta of 166 min. Upon administration through i.m., s.c. and oral route, the Cmax was reached between 30 and 90 min after inoculum and ranged between 7 and 4% of the administered dose. Organ distribution showed that most of the radioactivity was concentrated in kidneys and excreted in urine. From Sephadex G-10 chromatography, about 60% of the peptide recovered in the urine 4h after i.v. inoculum was intact, whereas it was more than 85% degraded when administered by other routes. The amount of intact peptide recovered in the urine correlated with the biological effectiveness through different routes, suggesting that the adjuvant effect in vivo is exerted by the intact peptide, rather than by its metabolites.

Amino Acid Sequence↗
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↗