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Biomedical subjects

V Bocci

Publications and source records attributed to V Bocci.

At least 73 records · Page 4Linked to original sources
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

Studies on tumor necrosis factor (TNF)--I. Pharmacokinetics of human recombinant TNF in rabbits and monkeys after intravenous administration.

By intravenous (bolus) administration of human recombinant tumor necrosis factor (2.5 X 10(6) units) into rabbits and monkeys it has been possible to follow its decay in the plasma and to determine the pharmacokinetic parameters. After labelling TNF with 125I, simultaneous determination of protein-bound radioactivity and bioactivity was carried out with the result that radioactivity decays somewhat slower than bio-activity suggesting that the use of the former tracer alone may underestimate TNF catabolism. Simultaneous determination of 125I-TNF in rabbit plasma and lymph after intravenous and subcutaneous administration indicated a lymph to plasma TNF concentration ratio of about 0.1 and 1 or more for the two routes, respectively.

Animals↗
PubMed1987

Studies on tumor necrosis factor (TNF). III. Plasma disappearance curves after intramuscular, subcutaneous, intraperitoneal, and oral administration of human recombinant TNF.

Since clinical trials with TNF as a therapeutic agent for cancer are in progress, in this study we have chosen to compare the metabolic characteristics of 125I-labeled and unlabeled RTNF after administration through IM, SC, IP and PO routes. Both RTNF and 125I-RTNF plasma concentration profiles showed an absorption phase and a biexponential decline common to all routes of administration. Moreover the pharmacokinetic analysis indicates that TNF blood levels following SC injection are rather similar to those seen after IM dose. No difference has been found in T max. In contrast, the Kel is apparently increased in the SC route, but the difference is not significant. While a prolonged absorption phase had been obtained after IP injection of RTNF, comparison of t 1/2 beta and Kel between IP and SC or IM route failed to reveal significant differences. Surprisingly some plasma TNF bioactivity has been detected following oral administration.

Administration, Oral↗
PubMed1987

Studies on tumor necrosis factor (TNF): II. Metabolic fate and distribution of human recombinant TNF.

We have evaluated the fate of cold and 125I- human recombinant tumor necrosis factor (RTNF) using isolated organs such as rabbit and monkey livers and rabbit kidney and lungs. We have also evaluated the body distribution of the total radioactivity after iv administration of 125I-RTNF in the rabbits. Monkey and rabbit livers play little catabolic role for RTNF. Lungs do not catabolize TNF at all, while the kidney appears to be the main catabolic organ. Accordingly, the body distribution of 125I-RTNF shows that most of the radioactivity is concentrated in the kidneys.

Animals↗
PubMed1986

The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma.

When human recombinant interferon-alpha 2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.

Animals↗
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↗
PubMed1986

The lymphatic route--II. Pharmacokinetics of human recombinant interferon-alpha 2 injected with albumin as a retarder in rabbits.

The aim of the present investigation was to define whether multisite subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human recombinant interferon-alpha 2 (rec. IFN-alpha 2) either in saline, human albumin (ALB) solution (4, 7 and 10% final concentrations), or in a solution containing 75 U of hyaluronidase, modified the pharmacokinetic parameters calculated from the IFN plasma levels. Plasma disappearance rates of rec. IFN-alpha 2 were measured in rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a three-pools mammillary model. This model was the basis for evaluating the absorption and distribution of rec. IFN-alpha 2 after s.c. administration. The increase of ALB concentration (from 4 to 10%) caused a significant reduction of the plasma IFN Cmax while both the mean residence time and the release time of IFN increased linearly with the ALB concentration. The data support the postulation that s.c. administration of albumin acts as an interstitial fluid expander and may favour absorption of IFN via lymphatics rather than blood capillaries. Improvement of therapeutic index of IFN by using this route remains to be shown in clinical trials.

Animals↗
PubMed1986

The lymphatic route--III. Pharmacokinetics of human natural interferon-beta injected with albumin as a retarder in rabbits.

The aim of the present investigation was to define whether multisite, subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human natural interferon-beta (nat. IFN-beta) either in saline, or in a human albumin (ALB) solution (10 and 13% final concentrations) modified the pharmacokinetic parameters calculated from the IFN plasma levels. Plasma disappearance rates of nat. INF-beta were measured in two rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a bi-exponential curve. The highest ALB concentration (13%) caused a significant reduction of the plasma IFN Cmax, a longer half-life, a three-fold increase of the area under curve (AUC value) and a marked decrease of the plasma clearance. Interestingly, the bio-availability of IFN was increased almost four-fold. The data suggest that, when nat. IFN-beta is injected subcutaneously, the presence of a high concentration of ALB may prevent its inactivation and may favour its absorption via lymphatics rather than blood capillaries. It is remarkable that by using this approach, low but constant IFN levels are maintained for as long as two days, a fact that may well increase the therapeutic index of IFN in patients.

Albumins↗
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↗