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Biomedical subjects

V Bocci

Publications and source records attributed to V Bocci.

At least 91 records · Page 5Linked to original sources
PubMed1985

The physiological interferon response: IV. Production of interferon by the perfused human placenta at term.

Human placentas at term, free of bacterial and viral diseases, have been perfused and maintained sterile for up to 13 hr. Several parameters indicate that the organs remained viable and released interferon into the perfusate in a progressive fashion. The amount of interferon was small and the individual variations indicate that there are "poor" and "good" placenta producers. Both interferons -alpha and -beta were produced with a prevalence of the latter type. The partial acid lability and the type heterogeneity suggest that under physiological conditions the placentas produce unusual interferons, the function of which remains speculative.

Amnion↗
PubMed1985

The physiologic interferon response. VI. Interferon activity in human plasma after a meal and drinking.

Interferon activity in plasma was found negligible in the morning and slightly increased in the afternoon. However, because of the wide variability of the results, the difference was not statistically significant even though the existence of a circadian rhythm appears possible. The afternoon increase of IFN activity could be at least in part due to increased abdominal lymphatic drainage following digestion and absorption. In fact, it has been shown that there is a significant transient increase in IFN plasma level 2 hours after a fat-rich meal or drinking 700 ml of water. IFN activity was due to acid-labile IFN-alpha. This is another, yet indirect, indication of the existence of the physiologic IFN response that entails a localized production of lymphomonokines with limited spillover in the circulation.

Adult↗
PubMed1985

The physiological interferon response. V. Antiviral activity present in rat lymph is neutralized by anti-mouse interferon-gamma antibodies.

By neutralization tests using anti-rat and mouse interferon (IFN) antibodies, we tested whether the antiviral activity present in abdominal lymph but absent in plasma of healthy rats, could be ascribed to IFN. Antimouse IFN-gamma antibodies neutralized the inhibitor completely while anti-rat IFN-alpha/beta antibodies did not. We conclude that rat lymph contains traces of IFN-gamma and that the antiviral activity is not due to low-density lipoproteins, immunoglobulins, or to cell-produced viral inhibitors. This finding extends previous observations on rabbit lymph and further supports the existence of a physiological low-level interferon response.

Animals↗
PubMed1984

Pulmonary catabolism of interferons: alveolar absorption of 125I-labeled human interferon alpha is accompanied by partial loss of biological activity.

The catabolism of interferon was examined in isolated rabbit lungs which were ventilated and perfused with homologous blood. Natural human interferon-alpha (HuIFN-alpha) from lymphoblastoid Namalwa cells or recombinant DNA-derived HuIFN-alpha 2 were labeled with 125I, mixed with an excess of the respective cold interferons and added to the perfusion blood. Protein-bound and acid-soluble radioactivity, as well as antiviral activity, were measured at regular time intervals. During the first 3 h of perfusion, only very small fractions of the interferons disappeared from the perfusate, irrespective of whether lungs were inserted in the perfusion system. This indicated that catabolism of interferons in the pulmonary circulation was negligible. On the other hand, when the interferons were instilled into the bronchial-alveolar tree, absorption of antiviral activity differed from that of acid-precipitable protein-associated radioactivity. While most of the radioactivity was transferred into the perfusate, only 2% of antiviral activity of natural HuIFN-alpha and 30% of that of HuIFN-alpha 2 were recovered in the perfusate. In both cases acid-soluble radioactivity in the system reached about 10%. Since radioiodide, instilled in the bronchial-alveolar tree, was transported rapidly into the perfusate, this type of analysis did not help in locating the site(s) of degradation. Alveolar macrophages did not catabolize or inactivate interferons in vitro.

Animals↗
PubMed1984

Evaluation of routes of administration of interferon in cancer: a review and a proposal.

Interferons are endowed with antiviral and antitumoral activities; the latter particularly has attracted attention, even though it remains uncertain whether it is preferentially due to a direct antiproliferative effect or to enhancement of host-mediated immune responses. Unfortunately, interferons administered in pharmacological doses produce considerable toxicity that is dose-related and that may require cessation of therapy. The administration of interferon has been carried out mostly by intravenous and intramuscular routes. High serum interferon titers have been expected to correlate with therapeutic efficacy. However, there is no such correlation, and certainly interferon levels in the interstitial fluid of target or effector cells would be more critical and informative. Moreover, because they are rapidly filtered by the kidneys, high serum titers are accompanied by considerable renal loss. Thus, several factors, one of which may be the unsuitability of administration routes, may explain the modest therapeutic efficacy of interferon so far observed in cancer. It must be emphasized that interferons and other biological response modifiers are pharmacodynamically unique substances able to elicit unpredictable responses; effects of these drugs depend on the nutritional and metabolic status and immune responsiveness of the host rather than simply on their plasma levels. After reviewing possible routes of administration, a new one, the lymphatic route, appears of interest. The basic strategy is to shift most of the interferon into the lymph pool minimizing direct absorption into the blood. In this way, the lymph/plasma ratio of interferon concentration will resemble that observed during the physiological response and will be greater than 1. Most of the injected interferon will then interact with the lymphoid system, even though eventually it will slowly drain into the blood pool. If the therapeutic index can be shown to be improved in patients, facilitated lymphatic absorption could become a preferential route for the administration of biological response modifiers.

Administration, Oral↗
PubMed1984

The physiological interferon response. II. Interferon is present in lymph but not in plasma of healthy rabbits.

If interferon is produced by the gut-associated lymphoid tissue of healthy rabbits under normal conditions and is not all bound in situ, it may spill over and be detectable in lymph. We therefore measured antiviral activity in lymph and plasma simultaneously. We found that antiviral activity was consistently measurable in abdominal and thoracic lymph but not in plasma or in the lymph collected from the hind leg duct. The antiviral activity was neither due to lipoproteins, nor immunoglobulins, nor to cell-produced viral inhibitors other than interferons. Extensive characterization of the antiviral activity indicated that the inhibitor is either rabbit interferon gamma or an acid-labile interferon alpha or a mixture; appropriate antisera will be necessary to resolve this uncertainty. The results support the view of the existence of a physiological interferon response.

Abdomen↗
PubMed1983

Renal metabolism of homologous serum interferon.

The metabolic behaviour of homologous native and desialylated serum and urinary interferons has been investigated by using an isolated and perfused rabbit kidney, the performance of which is comparable to that in vivo. Serum native and urinary interferons disappear from the plasma perfusate with a fractional turnover rate of 1.8 and 2% and half-lives of 3 and 35 min, respectively. Serum desialylated interferon disappears much more rapidly in keeping with the finding that the glomerular sieve poses less steric hindrance and electrophysical repulsion to the passage of less anionic proteins. These results confirm and extend our previous findings, which indicated that the kidneys have a predominant catabolic role and can explain to some extent the rapid disappearance of interferon from plasma.

Animals↗
PubMed1983

An analysis of the optimal conditions for perfusing an isolated rabbit kidney with homologous blood.

Isolated rabbit kidneys were perfused in a closed-circuit system with a number of media such a Krebs-Henseleit bicarbonate buffer with albumin, homologous platelet-free plasma, serum and whole blood. All of these media were unsatisfactory. In contrast, fresh blood deprived of platelets, leukocytes, floating lipoproteins, microaggregates and microclots did not cause vasoconstriction of the isolated kidney. Renal blood flow, glomerular filtration rate, urinary flow and glucose, cations and renal water reabsorption were approximately normal.

Absorption↗
PubMed1983

The physiological interferon response. I. Cells attached to intrauterine devices release interferon in vitro.

Cells attached to intrauterine devices (IUDs) release interferon (IFN) in the medium during incubation in vitro. Most of the IFN is released during the first hour suggesting that the cells had been previously induced and were probably already producing IFN in vivo. Characterization of the IFN indicates that most of it is of gamma-type with a trace of alpha. Production of IFN in the uterine fluid would represent a first example of the physiological IFN response and may serve to modulate some of the mechanisms preventing implantation of blastocyst. The actual presence of IFN in the uterine secretion remains to be demonstrated.

Culture Techniques↗
PubMed1983

Degradation of human 125I-interferon alpha by isolated perfused rabbit kidney and liver.

Rabbit livers and kidneys were isolated and perfused with homologous blood. After equilibration, human IFN alpha labeled with 125I and an excess of cold IFN alpha were added, and blood samples were withdrawn at predetermined times. Protein-bound and acid-soluble radioactivity together with biological (antiviral) activity were measured. Our results show that although liver exerts a minimal catabolism, the kidney filters and breaks down a considerable amount of IFN alpha. The parallelism between protein-bound radioactivity and biological activity decay curves indicates that IFN carefully labeled with 125I can be reliably used for metabolic investigations.

Animals↗
PubMed1982

The kidney is the main site of interferon catabolism.

The fate of human natural interferons alpha and beta and of recombinant (R) alpha 2 has been investigated by using an isolated and perfused rabbit kidney preparation with a normal physiological performance. A remarkable amount of IFN is filtrated in a monoexponential fashion, reabsorbed and very likely degraded in tubular cells with negligible excretion in the urine. The disappearance rate of HuRIFN-alpha 2 is higher than natural HuIFNs-alpha and beta and is in keeping with the lower molecular weight of RIFN-alpha 2. Differences in molecular charge or shape are probably responsible for the slightly reduced filtration of IFN-beta. Pharmacokinetic studies in animal models appear instructive and useful for devising improved dosage schedules in clinical trials.

Animals↗
PubMed1982

The role of liver in the catabolism of human alpha- and beta-interferon.

The susceptibility of human leukocyte (alpha), fibroblast (beta) and recombinant alpha-2-interferons to clearance by the isolated and perfused rabbit liver has been evaluated. Human leukocyte and recombinant alpha-2-interferons were stable and their initial levels were maintained in the perfusate even if they had been treated with neuraminidase, thus suggesting that alpha-interferons have no exposed sugars recognizable by hepatic binding proteins. On the other hand, native, and particularly desialylated human beta-interferon, underwent marked hepatic uptake confirming the importance of the liver as a catabolic site for glycosylated interferons.

Animals↗